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bad3d9a9196613ce6445313d77122a38 | https://www.forbes.com/sites/matthewherper/2011/06/12/scientists-create-a-living-laser/ | Scientists Create A Living Laser | Scientists Create A Living Laser
One of the first stories I was ever really proud of was on the history of green fluorescent protein, or GFP, a glowing protein found in jellyfish that can be used to make living things glow. I wasn't that surprised when GFP won the Nobel Prize a few years back. But this -- wow. Researchers have used GFP to create, literally, a living laser.
From Nature News:
Scientists have for the first time created laser light using living biological material: a single human cell and some jellyfish protein. "Lasers started from physics and are viewed as engineering devices," says Seok-Hyun Yun, an optical physicist at Harvard Medical School and Massachusetts General Hospital in Boston, who created the 'living laser' with his colleague Malte Gather. "This is the first time that we have used biological materials to build a laser and generate light from something that is living." The finding is reported today in Nature Photonics 1. via Human cell becomes living laser : Nature News.
I'm just going to make the obligatory X-Men reference (so that's how Cyclops shoots laser beams from his eyes) - and leave it at that.
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c808feeceaa72721be1a1da377a88936 | https://www.forbes.com/sites/matthewherper/2011/06/28/medical-journal-slams-medtronic-over-payments-to-doctors/ | Medical Journal Slams Medtronic Over Payments To Doctors | Medical Journal Slams Medtronic Over Payments To Doctors
A major medical journal has taken the dramatic step of publishing a series of articles alleging that side effects were downplayed or omitted in scientific articles about a Medtronic product used in spine surgery.
Instead, authors repeatedly asserted the device, called Infuse, caused few complications, according to the report by The Spine Journal, the official publication of the North American Spine Society. Moreover, the journal says, the authors of those often had received significant amounts of money from Medtronic.
On every large study of Infuse, at least one author had received at least $10 million in royalties, consulting, or other payments from Medtronic, according to Eugene Carragee, the Spine Journal’s editor.
“I was really shocked,” says Carragee, who is also a professor at Stanford University. “I wouldn’t have thought I was very naïve about this stuff. I’ve been doing this for 25 years.”
Side effects, including male infertility, neurological injury, and pain, were between 10 and 50 times as common they appeared to be in published studies, Carragee says. Medtronic disputes the way he arrived at these values and stands behind the safety and efficacy of Infuse.
Medtronic also says it was not directly involved in the preparation of the articles, and its new chief executive offered to help the Spine Society institute reforms. Two study authors contacted by Forbes defended their work.
Infuse combines a protein that causes bone to grow (a drug) with a device that delivers that protein to the spine. It is used instead of taking bone from the hip in spinal fusion surgeries in which extra bone is added to the spine to fuse parts of the back together, stabilizing it. These surgeries are sometimes necessary after injuries and in other cases, but there has been controversy about their use in less afflicted patients with serious back pain. Products including InFuse generated $868 million in sales for Medtronic in 2010, according to investment bank Sanford C. Bernstein.
The Food and Drug Administration issued a safety warning about Infuse in 2008. Carragee, the journal editor, says that he was also receiving a flood of letters saying that published studies about Infuse were “just not believable.” At first, Carragee says, he and his co-editors “shrugged.” He says: “You take what people tell you at face value, there’s not much you can do about it.” But at an editorial board meeting a year ago he changed his mind. “We said, ‘We have to do something.’”
Carragee asked the librarians at Stanford to pull every major study of Infuse, all the publicly available data from the FDA and other sources, and also information on conflicts of interest from Medtronic, which now publicly discloses payments to physicians, and from Senator Grassley, who had investigated the company. Then, working on a corkboard bulletin board above his garage on the Stanford campus, he and his colleagues compared the published articles side by side with data submitted to the FDA. They also looked at the compensation figures for the author of those articles.
“Like I said, I had read the letters some people had sent and [the allegations] seemed so outlandish that I didn’t believe it,” Carragee says. The compensation numbers some study authors were said to have received just seemed “crazy,” he says. But even in studies that followed 200 or 300 patients, he could see little evidence of side effects.
"That would make it safer than taking a short course of antibiotics and it just didn’t make any sense,” he says. “When we got the FDA data, it became clear that there were adverse events and some of pretty clear statistical significance as well. I was frankly shocked they hadn’t been reported in the published literature.”
The Spine Journal had already published one of its findings – a study conducted by Carragee saying that InFuse can cause a condition called retrograde ejaculation, which makes men infertile – but the bulk of the rest went online this evening. Carragee wrote an editorial in which he says there have been “years of living dangerously” with Infuse, and begins by quoting seven of the 13 Infuse studies he examined as they reported “no unanticipated device related adverse events,” “no complications, and “no adverse event that was specifically attributed” to the use of Infuse. The he quotes Hemingway: “Yes, isn’t it pretty to think so?”
His colleagues are just as harsh. Dan M. Spengler of Vanderbilt Medical Center in Nashville calls for changes to the way medical journals handle conflicts of interest. Sohail K. Mirza, of Dartmouth Hitchcock Medical Center, calls the FDA approval studies for the product “folly.”
“I don’t think this product should be removed from the market,” says Carragee. Some people, he says have spines that for various reasons won’t heal, and for them the risks are worth taking. “I do worry that most of the use has been in otherwise healthy people in their middle years who would have healed just fine. And they’ve been exposed to risk.”
In many ways, The Spine Journal’s articles seem like a replay of the drug safety controversies over Paxil, made by GlaxoSmithKline, Vioxx, made by Merck, and fen-phen, made by Wyeth, which is now part of Pfizer. But medical devices have traditionally been scrutinized less by regulators, and medical device makers, particularly in orthopedics and surgery, pay outside researchers far more than drug companies.
One reason for this is that in the device field, the very surgeon performing the operation is often an inventor, too. And that means he’s entitled to a royalty, which can be sizeable. In an appendix, the Spine Journal says that Thomas Zdeblick, a University of Wisconsin doctor who co-authored one paper, received $21 million over a period of years. Three other doctors are listed as receiving $11 million or more.
In an emailed response, Zdeblick wrote: “I do not believe that the initial Infuse studies, including those I took part in, understated the risks with Infuse.” He says retrograde ejaculation was not statistically significant, and that “scientific papers do not regard something as different unless it is statistically significant.” He also takes issue with the already published data by Carragee about the retrograde ejaculation side effect, and has written a detailed letter to the editor to The Spine Journal in which he writes that “to invite two commentaries alleging some type of cover-up, based on a flawed retrospective trial, is naïve and short-sided at best, and at worst inappropriate and irresponsible.”
The lead author of a study Zdeblick worked on, Scott Boden of Emory University, wrote in an email that conflicts had been disclosed to the scientific journal and that adverse events had been properly reported. “None of the peer reviewers, nor any of the Journal readers questioned our reporting of complications or any other aspect of those very first small human trials at the time of publication a decade ago or since,” Boden wrote. One of his papers won an international award.
New policies instituted since these papers would publish prevent any doctor who is receiving royalty payments for inventing devices from even participating in Medtronic clinical trials. “Medtronic is a fundamentally different company today than during the period of time when the Spine Journal published these,” says Chris O’Connell, who is in charge of the company’s spine business.
Richard Kuntz, Medtronic’s chief scientific officer, says he has found no evidence that Medtronic played a role in preparing the papers, aside from answering the questions of the outside academics. There were no ghostwriters, as has appeared to occur with other published studies.
“We’re not aware of any ghostwriters, we’re not aware of anybody preparing documents. It’s our understanding that this was completely written by the authors,” says Kuntz. Moreover, he argues that most of the omissions can be explained by the focus of the published paper and the increased scrutiny Medtronic gave data before they were submitted to the FDA. He says that the product label for Infuse accurately reflects its safety and efficacy.
Carragee sees a need for much more disclosure of financial conflicts. Among the steps being taken: instead of disclosing payments from companies as footnotes, The Spine Journal intends to put them in the body of articles. That means that if they are incorrect, it could stand as grounds for retraction. This could also lead readers to take the payments more seriously.
“I think that if you do a service for the company and the service is worth ‘X’ amount of money you should get ‘X’ amount of money,” says Carragee. “But if you’re writing advertising copy it should be in the advertising section.”
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f1198931448ae2149516dba9519e9cd5 | https://www.forbes.com/sites/matthewherper/2011/07/21/how-generics-and-obamacare-led-to-express-scripts-mammoth-purchase-of-medco/ | How Generics And ObamaCare Led To Express Scripts' Mammoth Purchase Of Medco | How Generics And ObamaCare Led To Express Scripts' Mammoth Purchase Of Medco
This morning, Express Scripts announced plans to buy rival Medco Health Solutions for $29 billion in cash and stock in a merger that will combine two of the largest managers of prescription drugs in the United States. It is the second-biggest deal of the year, after AT&T's proposed purchase of T-Mobile. The deal makes tremendous sense, because it will help the new, larger company weather what could be a difficult period in 2013 and 2014 when an drought of new cheap, generic drugs could hurt its sales.
Express Scripts and Medco are both pharmacy benefit managers or PBMs, a business that is largely unique to the United States and its employer-based health insurance system. PBMs help employers and insurers reduce the amount that people spend on prescription medicines. This is the industry that introduced, for instance, mail order pharmacy. The PBM negotiates lower prices with drug manufacturers, and takes a cut of the savings.
For years, the biggest source of saving money on drugs was switching people from brand medicines, which can cost thousands of dollars a year, to cheaper generics that either do the same or contain the same drug but can cost 90% less. PBMs actually make more profit on generics, too. If the PBM could get you to switch from brand Zocor to the generic version, simvastatin, or, better still, from branded Lipitor to generic simvastatin (both lower cholesterol) it was a win for both the PBM and your employer.
This changes, however, in a world where most drugs are generic. No longer is there a need to switch people to generic drugs, because they're likely to do so on their own. So instead of saving the employer and insurer money, the PBM could conceivably cost them cash.
Something like this scenario is rapidly approaching, as top-sellers like Lipitor, the best-selling drug on the planet, Zyprexa, for schizophrenia and bipolar disorder, and Plavix, for preventing heart attacks, all lose patent protection and go generic. Already, three-quarters of drug sales are for generics, and that number is going to sky rocket. This has gotten a lot of attention as a problem for the pharmaceutical companies that make those drugs (Pfizer, Eli Lilly, and the team of Bristol-Myers Squibb and Sanofi-Aventis, in the examples named) but it is also, ironically, a challenge for the PBMs.
This trough will happen in the second half of 2013 and 2014, says David Maris, an analyst who covers the healthcare industry at CLSA. He owns some Medco shares. He says that in his conversations with generic drug manufacturers, it has become clear that employers realize that Lipitor will be going generic, he says and they are going to ask the PBMs for more cost savings. "PBMS are going to get squeezed going forward," he says.
In roughly the same time period, the Affordable Care Act, (also known as ObamaCare), starts to kick in, Maris says. If the government is taking a bigger role in containing drug costs, that could actually decrease the need for PBMs, too.
Express Scripts spokesman Brian Henry wrote in an email that most of the drug spending in coming years will not come from traditional prescription drugs, but from new, high-priced specialty drugs for cancer, rheumatoid arthritis, and other relatively rare diseases that can cost tens or even hundreds of thousands of dollars per patient. This could increase as biosimilars – knockoffs of expensive biotech drugs like Amgen's Epogen or human growth hormone – begin to reach the market. And the Affordable Care Act will lead to an additional 30 million people under insurance, which could also help Express Scripts' growth. Medco's efforts in genomics, where the company has pioneered the use of gene tests in areas like prescribing the blood thinner warfarin, could also have an impact for the better for these companies.
But it is on the face of this that the deal does make sense. All those capabilities will improve with scale, if the merger is well-managed. And if 2013 and 2014 do turn out to be tough, a bigger battleship will have a better chance of weathering the storm. That is, assuming that antitrust officials have no problems combining two of the biggest names of the PBM space, and that controversies about having one company handle so much private data don't emerge. Henry says protecting patient privacy is "a fundamental commitment" for Express Scripts and the company has never been subject to state or federal disciplinary action related to laws on medical privacy.
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ec902f392c5773a0fa696c3a7b29764d | https://www.forbes.com/sites/matthewherper/2011/08/03/rallying-pharmas-rebels/ | Rallying Pharma's Rebels | Rallying Pharma's Rebels
Bernard Munos
From the 08.22.11 issue of Forbes Magazine: Bernard Munos has a radical idea to save the drug industry: Take bigger risks and cut R&D.
It’s no secret that the pharmaceutical industry is suffering. With too few breakthroughs and stagnant finances, the stocks of some of the industry’s biggest players, including Pfizer and Merck, are down 40% from a decade ago. The industry has cut 300,000 jobs in the last ten years as the number of new drugs making it to market slowed to a trickle.
Bernard Munos, 61, who worked in sales for 30 years at Eli Lilly, has spent the past decade studying pharmaceutical innovation. He thinks he has an answer to what ails Big Pharma: Cut research and development.
That’s just part of his prescription for changing how medicines are invented. Munos says the drug industry needs to spend research money in an entirely new way. Instead of chasing improvements to blockbuster drugs that help lots of people a little bit, it should focus on true breakthroughs that help patients a lot. And rather than do the research in-house, companies should close their labs and outsource the work to tiny, nimble startups that can explore bigger, crazier ideas.
“You cannot script innovation,” Munos says. “You cannot boil it down to a code of best practices. Because it is unpredictable and the opportunities in science do not match the opportunities in markets.”
Corey Goodman: "We need transformational change."
Munos' scorched-earth scheme is radical, but he’s fast gaining followers among a generation of entrepreneurial bioscientists fed up with the way the corporate world makes drugs. Corey Goodman, a former Pfizer executive and founder of biotechs such as Exelixis, a drug developer, and Second Genome, a genetics firm, is one of them. “These are things that the management of all the top companies knows,” he says. “Bernard put on the table that we don’t just need a Band-Aid. We need transformational change.”
At first glance Munos seems an odd revolutionary. After starting out in animal health, he helped restructure Lilly’s business in Latin America. He pioneered new ways of doing market research, then ran sales in Portugal, where his team broke sales records. He led marketing organizations in Eastern Europe and in Russia before returning to the U.S. as a special advisor to Lilly’s top executives.
Read More:Rallying Pharma's Rebels|The Best Drug Companies Of All Time|The Best Drug Companies Of The Decade|7 Steps To Pharma Innovation|6 Pharma Rebels
But after decades of fixing broken divisions and auditing managers, he was bored and yearned to address questions that had been “burning my tongue for years.” What was wrong with research? Why was productivity plunging as expenses soared? “We spend billions each year to get innovation, but where does innovation come from, and how do we get more of it?” asks Munos. “No one had a clue. Crude ideas about innovation pervaded not only the company but also the industry. This is an industry that spent tens of billions of dollars to create innovation but had not created tools to measure it.”
Looking for answers, he started pulling data from the Food & Drug Administration, from company filings with the Securities & Exchange Commission, from any other source he could find. After a decade of digging he’s come to the conclusion that the pharmaceutical industry “is imploding in slow motion” and could fail completely unless it adopts a whole new model of drug development.
Next: A New Model Of Drug Development
Munos’ first scientific paper, in 2006, was published in Nature Reviews Drug Discovery. It explored how
William Chin, Former Lilly Research Chief: "It's better to spend your money on something more risky... [+] and get a breakthrough."
the kind of open-source work that helped Linux become a credible threat to Microsoft Windows could also aid drug development. He acknowledged that unlike programmers, who need just a laptop, drug researchers needed laboratories and clinical trials, which are expensive. But he recommended that drug companies try making their resources available to outside scientists. Lilly actually tried this, screening 32,000 potential new drugs in 18 months. It wound up licensing three of them for further development.
But it was a 2009 paper that galvanized followers. Munos analyzed the records of more than 1,200 drug approvals going back to 1950. He found the amount of research money spent for each new drug approved has been increasing exponentially for years. In the 1970s for every $100 million or so drug companies put into research a new medicine would emerge. By 1990 this figure had risen to $500 million, and it has accelerated ever since. Munos says it hit $4 billion by 2009—and it is now careening toward $10 billion.
Yet there appears to be little correlation between cost and success. A new antibiotic invented by Optimer Pharmaceuticals cost only $175 million to develop this year. Pfizer tripled its R&D budget over the past decade—to a peak of $7 billion in 2006, more than any other company in the world—while the number of new medicines it brought to market declined. From 2001 to 2010 Pfizer brought to market only four drugs it had invented in its own labs.
So how can companies avoid tossing away billions on medicines that won’t work? By picking better targets. Munos says the companies that have done best made very big bets in untrammeled areas of pharmacology. Merck is the alltime champ, launching 56 new drugs since 1950. Its successes included the first statin cholesterol drugs Mevacor and Zocor, the first mumps vaccine and some of the first HIV drugs. At its peak it was run by a scientist, Roy P. Vagelos, who had previously served as its head of R&D and who deliberately avoided me-too drugs.
Read More:Rallying Pharma's Rebels|The Best Drug Companies Of All Time|The Best Drug Companies Of The Decade|7 Steps To Pharma Innovation|6 Pharma Rebels
Novartis adopted such a breakthrough-focused model in the 1990s and has launched 17 drugs in the past decade, 7 more than any other drugmaker. Part of the reason was former chief executive Daniel Vasella, a doctor who Munos says “understood what a breakthrough medicine was.” His central success was Gleevec, a treatment for a rare cancer. There was strong evidence it would work from the start, but the limited market worried company bean counters. Vasella pushed its development anyway. Gleevec became a $5-billion-a-year seller because of its $40,000 annual price and because it extended patients lives so much. Vasella left the CEO role last year.
Stephen Friend, of Sage BioNetworks, says biology is too complicated for any one company.
Munos also showed that mergers—endemic in the industry—don’t fix productivity and may actually hurt it. The 30 such deals done over the past 60 years didn’t boost research results at all. What correlated most with the number of new drugs approved was the total number of companies in the industry. More companies, more successful drugs. It didn’t matter how much they were spending. Munos thinks this is because individual companies must try new things to survive and risk breeds results.
This led to Munos’ most radical insight: Why keep researchers in house? Why not force them to form tiny companies of their own and outsource work to them?
Lots of people don’t like this idea, among them Joseph Jimenez, the current chief executive of Novartis. “Many companies are outsourcing R&D, or they’re cutting R&D significantly, and we don’t believe that is the right path,” he says. “The right path is to build capability in discovery and development, and strengthen our lead in innovation. It’s fundamental, it’s strategic, and we’re going to be the best in the world at it.”
John LaMattina, a senior partner at PureTech Ventures and a former head of R&D at Pfizer, agrees and says Munos’ approach is dead wrong. Research is actually improving, he says, with more drugs approved so far in 2011 than in all of 2010. Big, risky projects often blow up after billions of dollars have been spent. And some of the biggest successes, like Lipitor, were me-toos. “You can’t just be external,” he says. “You’ve still got to have a core of internal scientists.”
Next: Winning Converts
Zafgen CEO Tom Hughes: "Five years ago I would have told you this would be impossible."
But drug companies like Pfizer and Sanofi-Aventis seem to be listening to Munos, gingerly cutting R&D spending and trying to build outside networks. And a new generation of small firms are sprouting up to take on the work (see box, right).
It’s invigorating for researchers like Tom Hughes, who developed diabetes drugs at Novartis before becoming chief executive of Cambridge, Mass.-based Zafgen, a company developing weight-loss drugs that work by making the body burn more energy. His entire company is only three people. “If you had asked me five years ago I would have told you this would be impossible,” says Hughes. He doesn’t miss the “enormous inertia” of a big company and days wasted in meetings. “It is completely liberating. I’ve run very large groups, and I’ve enjoyed that, but when it comes to trying to prove a medicine, having the freedom to do what we need to do is liberating.”
Munos is thinking even bigger. He points to the Pentagon’s Defense Advanced Research Projects Agency, the innovation engine of the military, which developed GPS, night vision and biosensors with a staff of only 140 people—and vast imagination. What if drug companies acted that way? What areas of medicine might be revolutionized?
Munos retired from Lilly last year to start his own consulting business. He’s hopeful that Big Pharma is listening and will save itself. “You can change the world on a shoestring,” says Munos, “but you have to do the right things.”
Six Pharma Rebels
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Read More:Rallying Pharma's Rebels|The Best Drug Companies Of All Time|The Best Drug Companies Of The Decade|7 Steps To Pharma Innovation|6 Pharma Rebels
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fdfad85f5aef98addc38d554a2ce8e68 | https://www.forbes.com/sites/matthewherper/2011/12/29/five-predictions-for-biotech-and-medicine-in-2012/ | Five Predictions For Biotech And Medicine In 2012 | Five Predictions For Biotech And Medicine In 2012
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Continuing a proud Forbes tradition, here is what I see happening as we move forward through 2012.
1. We'll see more super-expensive drugs. Charging $100,000, $200,000, or even $500,000 per patient per year is the most successful strategy in the drug business. One case study: In 2008, the Joint Economic Committee of the Senate and House heard testimony alleging that drugs for rare, orphan diseases were getting too expensive. One parent testified that the treatment for her son had increased in price from $1,000 per vial to more than $30,000. There was controversy and bad press, but Acthar Gel's maker, Questcor Pharmaceuticals, has become one of the best-performing stocks in any business, up more than 2,500% over the past five years.
Biotech's other best recent performer is Alexion, which makes the drug Soliris for a rare blood cancer. It costs $500,000 per year for the average patient, making it the most expensive drug in the world. This strategy has its limits, and the high prices in some diseases are finally starting to meet resistance, particularly in cancer, where a de facto limit of $100,000 per patient per year seems have been reached. But the mass-market model no longer works. The vast majority of medicines are now cheap generics. No longer able to make money on volume, drug companies are going to focus more and more on price.
2. New genetic technologies will brave the valley of death. DNA sequencing is getting cheaper and making its way into hospitals. Some cancer patients (notably Christopher Hitchens and Steve Jobs) have used genetic tests to try and pick the right drugs for their tumors. But right now using DNA sequencing on patients is not making much money for companies that make DNA sequencers, such as market leader Illumina, and big funders like the National Institutes of Health are tightening their belts. The result is that the two publicly traded genomics upstarts, Pacific Biosciences of California and Complete Genomics, are trading below or near the value of the cash they have on hand.
The beneficiary so far has been Ion Torrent, the new sequencer maker bought by lab giant Life Technologies in 2010. It has been able to build a user base with its sequencing technology, an it could use this bulwark to launch a bigger attack on Illumina. The science will continue to advance. Whether it will happen because of these DNA sequencer companies or next generation efforts like Foundation Medicine, the Google Ventures-backed cancer sequencing startup, is anybody's guess.
3. Medical devices will face an even tougher environment. From heart-focused Medtronic and Boston Scientific to joint replacement makers like Stryker and Biomet, it's been an awful few years. Don't expect it to get better unless the industry can face its fundamental problem: too many of its devices don't face rigorous testing. The unfolding disaster over metal-on-metal hip implants that are deteriorating and needing to be replaced years before they should is just one example of this problem. Fixing it will require these companies to rethink how they invent and test products. It won't be easy, and the industry's response to a report from the Institute of Medicine this summer that suggested more large-scale clinical trials indicate that, as a group, these companies are not facing facts.
4. Health information technology will stall. There's a huge need for better computer systems to improve medicine, and the government is pushing hospitals to adopt them. But I tend to agree with analyst and fund manager Les Funtleyder at Miller, Tabak, who argues that hospitals are going to be slow to adopt new computer systems in 2012. What's really needed is a disruptive innovation, a computer system so good that it solves many of medicine's problems. We're probably not there yet.
5. Pharmacy benefit managers will struggle as their reason for existing vanishes. Companies like Medco and Express Scripts were created to help manage the explosion of mass-market drugs being churned out by Merck and Pfizer in the 1990s. Now they are merging, in part because they are going to get squeezed. Richard Evans of policy analysis firm Sovereign & Sector has called PBMS "the most compelling short story in healthcare" because they will lose ability to make money off of generics as insurers and the government move to new, better benchmarks for drug prices. When almost all drugs are generic, companies no longer need to hire somebody to switch people off the brand.
Bonus Prediction: India will eliminate polio. In a positive step for the effort to eradicate the virus that paralyzed Franklin Delano Roosevelt from the face of the planet, I'm going to predict that India will have managed to banish the disease. It's been many months, as I write this, since there has been a case there. If that keeps up, it will be a major victory for the effort, backed in part by the Bill & Melinda Gates Foundation, to battle this disease. Even if it's true, there's still a great deal of work to be done before this virus is gone.
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541eeacd277babaa7c6516f0d3a0c1d3 | https://www.forbes.com/sites/matthewherper/2012/02/09/the-best-drug-companies-of-the-past-15-years/ | The Best Drug Companies Of The Past 15 Years | The Best Drug Companies Of The Past 15 Years
Last summer, after writing a profile of Bernard Munos, who has made it his calling to understand what goes into pharmaceutical innovation, I posted two very simple tables based on Munos' data: of the drug companies that had approved the most drugs over the past decade, and over the past sixty years. I argued at the time (and still feel) that this is a pretty good surrogate for how good these companies were at being pharmaceutical firms -- because a drug company's main job is to invent new medicines and get them to patients.
Anyway, when I contacted Munos about a profile I was writing of the company that topped the ten-year list (that's Novartis, and you can read the story in the current issue of Forbes) he wrote back with measures over a different time frame -- 15 years. Novartis also winds up being tops in that window, too, with 21 new drugs (or new molecular entities, in pharma jargon) compared to 16 for Merck. I thought it was worth laying out those numbers too. What's interesting is that the analysis bridges that long-term time period and the past decade, when much of the drug business has been in an innovation drought. And however you do it, the same names end up near the top: not only Novartis but also J&J and Merck. I'll have more on this data soon -- including how much companies are spending per drug. For now I just want to thank Munos and his InnoThink Center for Research in Biomedical Innovation for providing this data.
Company Number of Drugs Novartis 21 Merck&Co 16 J&J 15 Pfizer 14 Wyeth 13 Bristol-Myers Squibb 11 Hoffmann-La Roche 11 Lilly 11 GlaxoSmithKline 10 Abbott (1) 9 Amgen 9 Pharmacia & Upjohn 9
Source: Bernard Munos, InnoThink Center for Research in Biomedical Innovation
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12c439d50f24116758709829f88e05a7 | https://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/ | The Truly Staggering Cost Of Inventing New Drugs | The Truly Staggering Cost Of Inventing New Drugs
Image by AFP/Getty Images via @daylife
During the Super Bowl, a representative of the pharmaceutical company Eli Lilly posted the on the company's corporate blog that the average cost of bringing a new drug to market is $1.3 billion, a price that would buy 371 Super Bowl ads, 16 million official NFL footballs, two pro football stadiums, pay of almost all NFL football players, and every seat in every NFL stadium for six weeks in a row. This is, of course, ludicrous.
The average drug developed by a major pharmaceutical company costs at least $4 billion, and it can be as much as $11 billion.
Research Spending Per New Drug Company Ticker Number of drugs approved R&D Spending Per Drug ($Mil) Total R&D Spending 1997-2011 ($Mil) AstraZeneca AZN 5 11,790.93 58,955 GlaxoSmithKline GSK 10 8,170.81 81,708 Sanofi SNY 8 7,909.26 63,274 Roche Holding AG RHHBY 11 7,803.77 85,841 Pfizer Inc. PFE 14 7,727.03 108,178 Johnson & Johnson JNJ 15 5,885.65 88,285 Eli Lilly & Co. LLY 11 4,577.04 50,347 Abbott Laboratories ABT 8 4,496.21 35,970 Merck & Co Inc MRK 16 4,209.99 67,360 Bristol-Myers Squibb Co. BMY 11 4,152.26 45,675 Novartis AG NVS 21 3,983.13 83,646 Amgen Inc. AMGN 9 3,692.14 33,229 Sources: InnoThink Center For Research In Biomedical Innovation; Thomson Reuters Fundamentals via FactSet Research Systems
The drug industry has been tossing around the $1 billion number for years. It is based largely on a study (supported by drug companies) by Joseph DiMasi of Tufts University. It's a nice number for the pharmaceutical industry, because it seems to justify the idea that medicines should be pricey (and increasingly, they can be very pricey, costing tens of thousands of dollars per patient per year) without making it seem that inventing new medicines is so expensive an endeavor as to be ultimately futile.
But as Bernard Munos of the InnoThink Center for Research In Biomedical Innovation has noted, just adjusting that estimate for current failure rates results in an estimate of $4 billion in research dollars spent for every drug that is approved. But Munos showed me another figure, where he divided each drug company's R&D budget by the average number of drugs approved. This was far more dramatic.
Wanting to make this even more rigorous, Forbes (that would be Scott DeCarlo and me) took Munos' count of drug approvals for the major pharmas and combined it with their research and development spending as reported in annual earnings filings going back fifteen years, pulled from a Thomson Reuters database using FactSet. We adjusted all the figures for inflation. Using both drug approvals and research budgets since 1997 keeps the estimates being skewed by short-term periods when R&D budgets or drug approvals changed dramatically.
The range of money spent is stunning. AstraZeneca has spent $12 billion in research money for every new drug approved, as much as the top-selling medicine ever generated in annual sales; Amgen spent just $3.7 billion. At $12 billion per drug, inventing medicines is a pretty unsustainable business. At $3.7 billion, you might just be able to make money (a new medicine can probably keep generating revenue for ten years; invent one a year at that rate and you'll do well).
There are lots of expenses here. A single clinical trial can cost $100 million at the high end, and the combined cost of manufacturing and clinical testing for some drugs has added up to $1 billion. But the main expense is failure. AstraZeneca does badly by this measure because it has had so few new drugs hit the market. Eli Lilly spent roughly the same amount on R&D, but got twice as many new medicines approved over that 15 year period, and so spent just $4.5 billion per drug.
Next: Slate's Bad Math
Why include failure in the cost? Right now, fewer than 1 in 10 medicines that start being tested in human clinical trials succeed. Some biotechnology companies do manage to make it to market without having to spend money on failed medicines – but only because other startups went bust trying to test other ideas.
Last year, an accounting in the journal BioSocieties claimed to take apart the earlier $1 billion figure and find that drug companies were really only spending $55 million on each new drugs. Picked up by Slate, this paper whittled down the number to $55 million. That's about a third of what was recorded in R&D by about the cheapest drug I can find – Optimer's new antibiotic Dificid for drug resistant clostriduim difficile bacteria. Total costs sunk? $175 million, for a product that delivered $24 million in sales during its first five months. If this is really just taxes and accounting games, I'd like it explained how it is that biotechnology companies so often manage to spend all of their cash.
The high cost of developing drugs shouldn't be a badge of honor for drug firms; there's no reason it has to be this expensive. And using the cost of research to justify the prices of prescription drugs was always a dumb move on the pharmaceutical industry's part. Just because something was expensive doesn't make it good. And another: many medicines are over-priced, but high-cost drugs are only a small part of our general health cost problem. Medicines are just among the easiest products to scapegoat because their prices are easier to track.
But if a drug company could promise to invent new medicines for $55 million a pop, its stock price would soar like Apple's. It really does cost billions of dollars to invent new medicines for heart disease, cancer, or diabetes. The reality is that the pharmaceutical business is in the grip of rising failure rates and rising costs. We can all only hope that new technologies and a better understanding of biology will turn things around.
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1863cf0531ebd1a2d69d598abd88fde8 | https://www.forbes.com/sites/matthewherper/2012/03/28/the-drug-industrys-blind-alley/ | The Drug Industry's Blind Alley | The Drug Industry's Blind Alley
Jack Scannell, an analyst at Sanford C. Bernstein who covers European pharma, is becoming a must read for anyone trying to figure out what has gone wrong with the drug industry's innovation engine. His latest note to clients is a prime example: a damning look at how the drug industry tried to automate itself, and wound up hurting its research labs.
During this time the industry switched from "phenotypic-based drug discovery" to targeted drugs that tried to find a gene that was causing a problem and hit it. Biotechs also pursued "biologic based discovery," favored by biotechs like Amgen, Biogen, and Genentech, in which signaling proteins in the body were copied or hit with antibodies. The result? Of the three approaches, target-based drug design was the least effective.
Writes Scannell:
[O]nly a minority of the most innovative drugs had their origins in target-based drug discovery; 17 out of 50. And of these 17, two drugs were eventually approved for indications that were entirely different to those that were intended at the start of the targetbased search. Bortezomib / Velcade was the product of a target-based search for drugs to treat musclewasting diseases, but found its use in multiple myeloma. Aprepitant / Emend was the product of a target-based search for agents to treat pain and depression, but ultimately found use as an anti-nausea agent. The majority of first-in-class drugs (33/50) had their origins in phenotypic screening or were derived by modifying natural substances that were already known to have some kind of biological action. In other words, the processes that the industry was trying to abandon proved to be more successful at delivering major innovation than the processes that the industry was trying to industrialize and optimize.
The numbers Scannell is quoting come from a paper called "How Were New Medicines Discovered?" by David Swinney and Jason Anthony in Nature Reviews Drug Discovery. One cause of the innovation drought that has hurt everyone from Pfizer to Eli Lilly to GlaxoSmithKline -- and, probably most of all, AstraZeneca, was the very attempt to improve drug discovery with combinatorial chemistry libraries and robots and genomics. The old ways might have been better. (Merck's Zetia, for example, was very much discovered the old way.) It's a sobering thought. But Scannell thinks it should be a comfort, not a curse, at this point. "An industry that has made fixable errors," he writes, "is preferable to one that has low R&D productivity despite having done all the right things."
Update: In response to the questions below, here are the charts from Scannell's note that show the proportion of drugs derived from target-based screens.
Source: Bernstein Research
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77fd5ffa9ac578bd77c9aa574abb9dd1 | https://www.forbes.com/sites/matthewherper/2012/05/01/jim-watson-who-discovered-dnas-structure-picks-his-favorite-gene/ | DNA Discoverer Jim Watson Picks His Favorite Gene | DNA Discoverer Jim Watson Picks His Favorite Gene
Nobel laureate Dr. James D. Watson (Photo credit: Wikipedia)
In Forbes' "Love Only One" feature, which is returning after a long hiatus, we ask the biggest luminaries in different fields for their top picks in everything from stocks to gadgets. Here, we ask Nobel laureate James Watson, the co-discoverer of the structure of DNA and one of the first people to have his genome sequenced, to pick his favorite gene. From the May 21, 2012, issue of Forbes Magazine.
"One gene fascinates me: POMC, on chromosome 2, which is a recipe for a protein called pro-opiomelanocortin. In the body it gets broken up into different proteins, including melanotropin, which makes the skin darker when you’ve been in the sun, and beta-endorphin, a natural opioid that makes you feel satisfied after eating and also causes the ‘runner’s high.’ It’s the only gene I know whose very structure is an implicit biological message: Happiness is a reward for doing what we should be doing—for being in the sun and making vitamin D, for exercising and for bringing nutrients into our bodies. Eons ago these messages were delivered by the genes of our vertebrate ancestors on this planet. Now they are passed down to us.”
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f16952e147e209f15d73c21da0334a28 | https://www.forbes.com/sites/matthewherper/2012/05/07/a-fathers-battle-to-change-the-future-of-brain-research/ | A Father's Battle To Change The Future Of Brain Research | A Father's Battle To Change The Future Of Brain Research
This story appears in the May 2012 issue of ForbesLife under the headline "Brain Trust."
Garen and Shari Staglin. Photograph by Eric Millette
At a recent lunch organized by Jeffrey Lieberman, Columbia University’s chairman of psychiatry, New York’s top neurological researchers gathered to meet the nonprofit team they had been told would transform the very nature of their jobs.
Patrick Kennedy (Ted’s son and a former Congressman from Rhode Island), the cochairman and public face of the charity One Mind for Research, kicked off the meeting by deeming the assembled luminaries “today’s astronauts.” General Pete Chiarelli, One Mind’s new CEO—recruited from his just-completed stint as the U.S. Army’s vice chief of staff—discussed the astonishing increase in post-traumatic stress disorder and traumatic brain injury seen in soldiers returning from Afghanistan and Iraq.
The key figure at the gathering, though, was Garen Staglin, the quiet force behind One Mind and two other mental health charities, all of which have helped promote psychiatric-drug research even as big pharmaceutical firms have scaled back their efforts. Despite pressure on the National Institutes of Health’s budget, Staglin averred, it was still possible to get the government to open its coffers—if politicians could only be made to recognize the toll taken by mental illness, from the Alzheimer’s striking aging baby boomers to the autism afflicting their grandchildren.
“The time is now. We can move from treatments to preventions to early diagnosis and develop cures,” Staglin told the group.
His talk unleashed the floodgates: Scientists doing research on nerve signaling in worms were now trading ideas with those who study how concussions can lead to Alzheimer’s-like brain tangles. Drug-company researchers conferred with academics trying to treat mental illness with electromagnetic fields. The room came alive with ideas.
Such connections in the service of a larger good are something of a Staglin hallmark. One Mind for Research was in part Kennedy’s brainchild, but Staglin has actually made it work, enlisting big partners, including Johnson & Johnson, General Electric, IBM, and Eli Lilly, and recruiting Chiarelli, who spurned more lucrative opportunities to become the group’s chief executive. Stag-lin has long been an “integrator” in the fight against mental illness: someone who gets people who otherwise might never speak to work together. (At times, he has forced competitive academics to collaborate, warning them they won’t get grants from his charities otherwise.)
“With brain research, we’re where cancer was 20 years ago,” Staglin says. “There’s no American Brain Society. The American Cancer Society has unified the public behind the idea that we can cure the disease, not just from government but also private sources. We need to do the same.”
Staglin’s journey to the forefront of mental-illness research was circuitous. He studied electrical and nuclear engineering at UCLA (he met his wife, Shari, on a blind date there), and got his MBA from Stanford. His goal was to be a manager, and he got his wish—albeit in Vietnam, where he spent 18 months on a Navy ship directing rescue helicopters. “You learn a lot about yourself in a short time when you’re 23 and managing men who are much older,” he says.
Back home, he worked for Robert McNamara in the Defense Department’s famed “whiz kids” systems-analysis group before moving into venture capital. One of his early jobs involved running an account for Tom Watson Jr., the legendary IBM chief executive, investing in laser manufacturer Spectra-Physics and Applied Materials. Staglin later helped run Safelite AutoGlass (which he sold in 1993), eOne Global, and Solera, the automotive IT firm that went public in 2007. His fortune secure, he and Shari made a major life investment, launching Staglin Family Vineyard in Napa Valley in 1985.
Casual days of managing their investments and their outstanding Chardonnay vines seemed their destiny—but they soon discovered their true calling via their son, Brandon. With near-perfect SAT scores, Brandon was accepted to every college to which he applied, choosing Dartmouth. In 1990, after his freshman year, he came home obsessing over a breakup and lamenting how hard it was to find a summer job. Then, when Staglin and Shari were on a business trip to France, something went badly wrong.
“I’d been having symptoms,” Brandon recalls. “Weird pressures in my head, voices that weren’t mine. I could hear, ‘Brandon, you’re a mixed-up kid.’ ” He felt a strange lightness around his right eye and couldn’t recognize his emotions. He’d stay awake for days, but hospitals sent him home. In one instance, the police did likewise: Having pulled him over on suspicion of DUI, they were perplexed that he was fully sober. At last, a friend checked him into a psychiatric hospital. “They knew they couldn’t leave me like this,” Brandon says. “There was something wrong with my mind.”
He was finally diagnosed with schizophrenia. “It was devastating,” says Staglin, who took six months off to help his son learn to cope. Prescribed the antipsychotic drug Clozaril, an emotionally deadened Brandon returned to Dartmouth six months later. His parents, confounded by his disease and deploring its stigma in equal measure, decided to go public with their family’s situation in 1995.
“We needed to be putting money into this, but where do you put it?” says Shari. The lovely setting of the couple’s winery and vineyard gave them the idea to host a benefit concert. Friends, including famed Chicago chef Charlie Trotter, provided services gratis; the Staglins hired musicians from the San Francisco Ballet. To disburse the funds, they founded the International Mental Health Research Organization, which has since raised $140 million for schizophrenia research.
Brandon’s struggle is emblematic of the problems of this complex illness, and the promise that additional research portends: After graduating from Dartmouth, he had to drop out of his aerospace engineering program at MIT; the Clozaril was causing him to sleep 12 hours a night. Eventually, he identified a cocktail of medicines—Abilify, Risperdal, and Ativan—that worked better. He began to get involved with his parents’ work: designing their websites, overseeing grant programs, and, finally, giving public talks. A few years ago, he fell in love and got married. “It’s taken me 20 years to accept that this is part of who I am,” he says.
His saga is a microcosm of this enormous yet largely hidden problem. On current trends, Alzheimer’s alone will cost $1.1 trillion by 2050, according to the Alzheimer’s Association, yet pharmaceutical giants such as Pfizer, AstraZeneca, and Novartis are scaling back their psychiatric research. Thousands of soldiers return home damaged, but critics often scapegoat military doctors. “I’ve seen kids missing two legs run the Marine Corps marathon,” Chiarelli says. “But the same doctors are criticized for the way they take care of PTSD.”
One Mind aims to boost by nearly 20 percent the $8 billion the government and drug companies annually spend researching mental illness. Staglin’s talent for cross-coordination plays a big part—Johnson & Johnson has donated a medical researcher to work full-time as One Mind’s chief scientist, and PricewaterhouseCoopers is putting together a comprehensive estimate of how much brain diseases cost society. Meanwhile, One Mind has begun the largest study ever undertaken of traumatic brain injuries and PTSD.
“If it’s successful, One Mind will not only raise money but create an ethos of data sharing,” says Steven Hyman, a former head of the National Institute of Mental Health, who chairs the organization’s scientific advisory board. “It will actually make the world a better place.”
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5f739917519a429aab35bb88e2813733 | https://www.forbes.com/sites/matthewherper/2012/12/27/the-most-important-new-drug-of-2012/?partner=yahootix | The Most Important New Drug Of 2012 | The Most Important New Drug Of 2012
The Food and Drug Administration looks set for a great 2012; with a few days left to go, it has approved 40 new drugs and vaccines, one of the most impressive totals ever, according to data from Pharmaceutical Approvals Monthly and FDA press releases. In this haul, one medicine stands out for its scientific and medical importance.
Kalydeco, for cystic fibrosis, is a triumph of genetics and drug development, the first medicine to directly affect the genetic defect that causes the disease. It will only help 4% of the 70,000 people who suffer from declining lung function, damaged pancreases, and shortened lives due to CF worldwide, but in those few it has a dramatic effect. It makes medical history for three reasons:
It's a genomics triumph: Francis Collins, later famous for heading the Human Genome Project and then the National Institutes of Health, discovered the gene that, when mutated, causes cystic fibrosis 23 years ago. Kalydeco is the first drug to directly affect the defects caused by these mutations, leading to improvements in patients' lung function. A patient group powered its development: Kalydeco would probably not exist were it not for the Cystic Fibrosis Foundation, which funded its early development at Vertex and gets a royalty on the drug. This success paved the way for other disease foundations including the Michael J. Fox Foundation, Myelin Repair, and the Multiple Myeloma Research Foundation. Its price: Kalydeco, given alone, will only help a few thousand patients the world over. Like other drugs for very rare diseases, its price is very high: $294,000 per patient per year.
Vertex shares have fallen 37% from their high earlier this year because of doubts by investors that Vertex will succeed in its attempts to dramatically expand Kalydeco's use by combining it with a second drug that will make it work in CF patients whose disease is caused by other, more common, mutations. Initial results were very promising, but then Vertex had to restate them. Sales of its best-seller, Incivek for hepatitis C, are dropping. But whatever you think of Vertex shares, Kalydeco is already a success, with $113 million in sales in the first nine months of 2012.
Kalydeco was not the only important drug this year, in which the FDA also approved the first flu vaccine made in cells, not chicken eggs (that's a Novartis product) and several important cancer drugs including Onyx's Kyprolis, Medivation's Xtandi, and Roche's Perjeta. Nor is it the most commercially important -- that honor goes to Gilead's Stribild combination pill for HIV, which could help preserve that company's HIV franchise through patent expirations. But it's probably the most exciting as a harbinger of drugs to come.
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7253f88bb7afe53d2ed5dab8416b0fa0 | https://www.forbes.com/sites/matthewherper/2013/02/05/forbes-healthcare-summit-using-big-data-to-make-patients-better/ | Forbes Healthcare Summit: Using Big Data To Make Patients Better | Forbes Healthcare Summit: Using Big Data To Make Patients Better
This is one of a series of posts that presents, nearly in its entirety, the first annual Forbes Healthcare Summit that was held on December 5, 2012, in the Allen Room at Jazz at Lincoln Center in Manhattan. Two hundred and thirty-two executives, entrepreneurs, thinkers and policy makers gathered to talk, trade ideas, and grapple with a big-picture conversation about the health care system. Video of almost every single panel is included.
Panel Title: Using Big Data to Make Patients Better and Help Guide Doctors
Medicine is often without the kind of data-monitoring used for quality control in other businesses. Can new sources of data help improve patient care?
Moderator: Glen de Vries, Co-founder and President, Medidata
Panelists: Harlan Krumholz, Professor of Medicine, Epidemiology, and Public Health, Yale University School of Medicine
Andy Slavitt, Group Executive Vice President, Optum
Peter Tippett, Chief Medical Officer, Verizon
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The First Annual Forbes Healthcare Summit On December 25, 2012, 232 executives, policy-makers, and thinkers -including Michael J. Fox, above -- gathered in Manhattan to take a broad look at the health care system.
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093cb8554ed9de1bdaf40bf3df8aaa10 | https://www.forbes.com/sites/matthewherper/2013/02/06/biogen-to-buy-elans-tysabri-rights-for-3-25-billion/ | In Wise Move, Biogen Spends $3.25 Billion For Rest Of Tysabri. Now What Happens To Elan? | In Wise Move, Biogen Spends $3.25 Billion For Rest Of Tysabri. Now What Happens To Elan?
Biogen Idec will purchase all rights to the blockbuster multiple sclerosis drug Tysabri from its partner, Elan Pharmaceuticals, for $3.25 billion, adding a capstone to a long and tangled journey for a drug that was once withdrawn from the market.
Elan, which originally developed the drug, will still receive a substantial royalty. For the first twelve months after the deal closes, it will amount to 12% of annual Tysabri sales. After that it will leap to 18% of sales up to $2 billion and 25% of sales over $2 billion. (If Tysabri were to generate $2.5 billion in sales, Elan would receive $485 million.) Last year, Tysabri sales were $1.6 billion, up 8% from 2011.
Biogen Idec shares were up nearly 6$ to $166.48 in pre-market trading. Elan shares inched down 3.44% to $10.12.
Biogen Idec says the deal will be boost its earnings from the very first year, increasing earnings according to generally accepted accounting principles (GAAP) by 0.20 to $0.30 in 2013 and non-GAAP earnings, used by Wall Street analysts to model the company's base business, by $0.50 to $0.60 per share in 2013. The boost to earnings will continue thereafter.
Until now, Elan was contributing financially to the marketing of Tysabri and had a say in the strategy for the drug. But it did not actively field sales reps on the ground, says Tony Kingsley, Biogen Idec’s head of marketing.
“We have been the commercial lead in the product,” says Kingsley. “We’re the only people with commercial resources, the only people with marketers and sellers we’ve worked jointly on the strategy with Elan.”
Tysabri, which is infused monthly, was approved in 2004 and is more effective than other drugs at preventing MS relapses that destroy the connections between nerves in the brain and spinal cord. It was originally withdrawn because it also raised the risk of a rare but deadly brain infection. Biogen and Elan successfully reintroduced the drug. More recently, sales have increased because the companies identified a blood test that could help screen out patients at risk of that infection.
By owning full rights to the drug, Biogen will be able to more easily streamline its marketing with other MS drugs, including Avonex and Tecfidera, formerly known as BG-12, a pill that is awaiting FDA approval.
In 2009, Elan sold 25% of the interest in an Alzheimer’s medicine to J&J; that drug has since failed. In 2011, Elan sold its drug delivery business to Alkermes for $960 million. Many investors had speculated that Biogen Idec might buy Elan outright. Instead it paid about half of Elan’s market capitalization, plus a substantial royalty. Last year, it spun off its research arm into a new company, Prothena.
What happens to Elan now? In a prepared statement, chief executive Kelly Martin said the deal "provides Elan with significant strategic flexibility. Future actions will be guided by our consistent and multi-year approach of dynamic risk/reward assessment of business opportunities. We are enthusiastic about the market opportunities around the globe and remain flexible and creative about the manner in which we would participate in those opportunities.” That sounds, to me, as if he really isn't sure.
In a note to his clients this morning, ISI Group biotech and pharma analyst Mark Schoenebaum wrote that he expects Biogen stock to trade up on the deal even if it looks expensive because investors will give Biogen's management the benefit of the doubt when it comes to all things MS. If the company really believes that Tysabri will be bigger than Wall Street expects, Wall Street will probably be ready to believe that. He also writes that he believes that Biogen has always "coveted" Elan's half of Tysabri, because while its Tecfidera pill, which has not yet launched, could become the dominant MS drug, it will lose patent protection in the mid-2020s, and sales will go to zero. Tysabri, by contrast, will probably never face true generic competition, because it is a type of drug called a monoclonal antibody that will be much harder to produce cheaply.
This story has been updated from its original version.
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6476861f403d3c9cdec73e8ed01b366a | https://www.forbes.com/sites/matthewherper/2013/02/08/more-polio-workers-killed/ | More Polio Workers Killed | More Polio Workers Killed
This is a global tragedy. There are others to blame aside from the militants in Kano. The U.S. government carries blame for using a ruse including flu vaccines to try and catch Osama Bin Laden. Perhaps Pfizer's experiments with Trovan in Nigeria, which became controversial, have helped poison the well.
But if we can't get vaccine to children in Pakistan, Afghanistan, and Nigeria, the three countries where polio is still endemic, the disease, eradicated in the rest of the world, will come back. Decades of work by Rotary International and, more recently, by Bill Gates, will be for nothing. This is a giant tragedy, not just because heroic workers who only want to help kids and end disease are being killed but because we may fail to completely eradicate a scourge when we are so very, very close.
(Reuters) - Gunmen on motorbikes shot dead nine health workers who were administering polio vaccinations in two separate attacks in Nigeria's main northern city of Kano on Friday, police said. No one claimed responsibility but Islamist militant group Boko Haram, a sect which has condemned the use of Western medicine, has been blamed for carrying out a spate of assaults on security forces in the city in recent weeks. Some influential Muslim leaders in Kano openly oppose polio vaccination, saying it is a conspiracy against Muslim children. The attacks will hit efforts by global health organizations to clear Nigeria's mostly-Muslim north of polio; a virus that can cause irreversible paralysis within hours of infection. It is the second time this year that polio workers have come under attack by Islamist militants after gunmen killed aid workers tackling the disease in Pakistan last month. via Gunmen kill nine polio health workers in Nigeria | Reuters.
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2e349c50abcb566037e8f848ec98fa2f | https://www.forbes.com/sites/matthewherper/2013/02/19/a-graphic-that-drives-home-how-vaccines-have-changed-our-world/ | How Vaccines Have Changed Our World In One Graphic | How Vaccines Have Changed Our World In One Graphic
The data in this graphic come from the web site of the Centers for Disease Control & Prevention, but a graphic designer in Purchase, N.Y., named Leon Farrant has created a graphic that drives home what the data mean.
Below is a look at the past morbidity (how many people became sick) of what were once very common infectious diseases, and the current morbidity in the U.S. There's no smallpox and no polio, almost no measles, dramatically less chickenpox (also known as varicella) and H. influenza (that's not flu, but a bacteria that can cause deadly meningitis.
This should drive home how effective the common childhood inoculations, made by Merck, Sanofi, GlaxoSmithKline, and Novartis, are. The pneumococcal vaccine, made by Pfizer, has resulted in dramatic drops in meningitis and pneumonia. When Bristol-Myers Squibb lost a patent case related to its hepatitis B drug the other week, investors shrugged, because children here are vaccinated against hepatitis B, so this isn't a big market. The pertussis (whooping cough) vaccine has been failing us, because immunity against it fades. But there's still a dramatic reduction in what was once a common disease.
You can see more of Farrant's work here.
vaccine infographic created by Leon Farrant
Update: To be clear, these data represent data collected in 2007 on past incidence of these diseases. This was published here, in the Journal of the American Medical Association. The current data are annualized cases for 2010, per the link to the original data that I had included above.
More on vaccines:
How Pneumococcal Vaccine Nearly Eliminated A Killer Of Infants
The Gardasil Problem: How The U.S. Lost Faith In A Promising Vaccine
One Of My Favorite Charts On The Power Of Vaccines
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53f786c347f456102bbeacf039c54e31 | https://www.forbes.com/sites/matthewherper/2013/02/27/how-a-creative-biotech-vc-exit-looks-in-2013/ | What A Creative Biotech VC Exit Looks Like In 2013 | What A Creative Biotech VC Exit Looks Like In 2013
The lack of a strong IPO market makes life tougher for biotech venture capitalists. Boston's Third Rock Ventures has done some creative deals to try to get a return. Details on one interesting one were revealed in the purchase of a company called Lotus Tissue Repair by Shire. Details were revealed in a recent 10-K:
Acquisition of Lotus Tissue Repair, Inc (“Lotus”) On February 12, 2013 Shire completed the acquisition of 100% of the outstanding share capital of Lotus, a privately held biotechnology company based in Cambridge, MA. Cash consideration paid on closing by the Company was $49.3 million. Further contingent cash consideration of up to $275.0 million may be payable by the Company in future periods, dependent upon the achievement of certain safety and development milestones. Lotus is developing a proprietary recombinant form of human collagen Type VII as the first and only intravenous protein replacement therapy currently being investigated for the treatment of Dystrophic Epidermolysis Bullosa (“DEB”). DEB is a devastating orphan disease for which there is no currently approved treatment option other than palliative care. The acquisition adds a late stage pre-clinical product for the treatment of DEB with global rights to Shire’s HGT pipeline. This acquisition is complementary to Shire’s existing investment in developing ABH001, which is currently being investigated as a dermal substitute therapy for the treatment of non-healing wounds in patients with EB. The acquisition of Lotus will be accounted for as a purchase business combination. The assets acquired and the liabilities assumed from Lotus will be recorded at the date of acquisition, at their fair value. Shire’s consolidated financial statements will reflect these fair values at, and the results of Lotus will be included in Shire’s consolidated statement of income from, February 12, 2013. As the initial accounting for the business combination has not yet been completed, further disclosure relating to this acquisition will be included in the Company’s Form 10-Q for the three months ended March 31, 2013. In the year to December 31, 2012 the Company expensed costs of $0.5 million relating to the Lotus acquisition, which have been recorded within Integration and acquisition costs in the Company’s consolidated statement of income.
According to a Third Rock spokesman, the company made a $26 million commitment to Lotus in 2011 and at the time of the sale was the sole investor with a 73% ownership stake. That means the firm already made a $10 million return. If the technology works, it could get future payouts totaling 20 times its initial investment. That's a pretty good portrait of a lot of deals: an ok payout now to erase the downside, with the possibility of much more later.
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f8e8627eb6a2f50ebe4bc9b2d256deee | https://www.forbes.com/sites/matthewherper/2013/05/03/the-plan-b-controversy-actually-we-do-let-kids-make-some-medical-decisions/ | The Plan B Absurdity: Emergency Contraception Is Treated Like A Drug That Could Be Abused | The Plan B Absurdity: Emergency Contraception Is Treated Like A Drug That Could Be Abused
(Credit: Dmitry Kalinovsky)
One of the main objections I've heard against expanding over-the-counter access to Plan B, the morning after pill, is expressed here by Penny Nance, CEO and President of Concerned Women for America (CWA):
“It makes no sense that kids need parental permission to take aspirin at school, but they’re free to buy and administer Plan B...The same ‘women’s rights’ advocates who want every decision to be between ‘a woman and her doctor’ are now eliminating the doctor, isolating young girls in situations that need adult guidance. If health officials continue to push women to make ‘Plan B’ their ‘Plan A,’ we have truly put politics and ‘progress’ ahead of the health of women and, now, our kids.” via Critics and Supporters React To Decision to Expand OTC Access to Plan B | TIME.com.
Stated differently, I've heard people assert that we don't allow kids to make medical decisions on their own, and that's why they should have to show identification in order to purchase the morning after pill in order to reduce the odds or pregnancy after unprotected sex.
The problem with this argument is that although an adolescent might not be able to bring an aspirin to school, she can walk to the drug store and buy one there without restrictions, even though aspirin can cause gastrointestinal bleeding. The same goes for Advil and Aleve (also can cause GI bleeding), Tylenol (liver damage) and antihistamines like Benadryl and Chlor-Trimeton, which impair judgement and could lead to accidents. And, honestly, there are no age restrictions on just about every over-the-counter medicine in the drug store.
I checked with CVS, the giant pharmacy chain, on what other medicines require proof of age. The answer? Three types of drugs:
cough/cold products that contain dextromethorphan (DXM) products containing pseudoephedrine (PSE) emergency contraception.
They also age-restrict alcohol, tobacco and compressed air dusters. So kids can’t get Robitussin or pseudophedrine, the active ingredient in Sudafed which can be used to make amphetamine. But they can get most other medicines. There are plenty of medicines that are probably riskier than the morning after pill that we don't restrict to protect children.
Plan B One Step is being held to different standards because it involves sex, and reproduction. But if the FDA's judgement is that the medicine should be available to girls as young as 15, what is the benefit of forcing those girls to show ID? Research funded by TEVA, Plan B's maker, showed that age wasn't correlated with whether women or teenage girls could understand the product's medical labeling. The American Medical Association backed making the product over-the-counter in 2000, a year after it was approved. An FDA expert panel that voted 23 to 4 that the pill should be made available over-the-counter in 2004.
Trying to not follow through on those scientific recommendations has harmed one of our most important regulators-- the FDA. The FDA had a tradition of not having the commissioner, a political appointee, make decisions about individual drugs --until that policy was broken to keep Plan B from being sold over the counter during George W. Bush's presidency. The White House never over-ruled the FDA -- until the Obama administration did last year. Despite this, sales of over-the-counter emergency contraception, including Plan B and several generic competitors, have grown from $173 million in 2007 to $279 million last year, according to drug data consultancy IMS Health.
It's not the role of drug stores to try and force conversations between teenagers and parents about sexual behavior, just as it's not the role of politicians or their appointees to make scientific decisions about the benefits of drugs. Staffers at the FDA have repeatedly decided that Plan B is safe and effective enough for routine use. Do we really want to set the precedent of letting politicians make those decisions instead?
Gallery: Global 2000: World's Biggest Drug Companies 2013 11 images View gallery
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c95b1d0a8ae8ed53519bc65fb5296445 | https://www.forbes.com/sites/matthewherper/2013/05/08/why-psychiatrys-seismic-shift-will-happen-slowly/ | Why Psychiatry's Seismic Shift Will Happen Slowly | Why Psychiatry's Seismic Shift Will Happen Slowly
Thomas R. Insel, Director, National Institute of Mental Health. (Photo credit: Wikipedia)
Last week, Thomas Insel, Director of the National Institute of Mental Health, published a blog post that outlined a new approach for deciding what psychiatry research the U.S. government would fund. No longer, he wrote, would the NIMH rely on the Diagnostic and Statistical Manual of Mental Disorders, the collection of symptoms used by psychiatrists to diagnose depression, bipolar disorder, schizophrenia, and other ailments, as its “gold standard” for categorizing patients in research studies. He wrote:
While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.
As a result of this, he wrote, the NIMH “will be re-orienting its research away from DSM categories." Instead, it would be encouraging medical researchers to frame their studies using a still nascent classification system being developed by the NIMH, called the Research Domain Criteria (RDoC).
The reaction from the blogosphere was swift and loud as journalists and bloggers interpreted the decision as a swipe against the fifth edition of the DSM (called the DSM-5) and the American Psychiatric Association, which compiles it. Mindhacks wrote that the NIMH was “abandoning the DSM” and called the move “potentially seismic.” New Scientist called it a “bombshell” and said the DSM was being “denounced.” The Verge also went with the headline that the NIMH was abandoning the “controversial bible” of psychiatry. John Horgan at Scientific American wrote that psychiatry was in crisis as Insel rejected its Bible and replaced it with nothing.
There were also some more nuanced comments, from Neurocritic and 1 Boring Old Man, noting that this was not a shift so much as a continuation of the line of thinking that had been presented previously by both Insel and the APA itself. But the DSM-5 has been beset by controversy, partly because Allen Frances, a prominent psychiatrist who worked on previous editions, has been publicly decrying the way the new edition of the manual was put together. And a fight between the country's largest psychiatric organization and the institute that decides which psychiatric projects get government money was too good to pass up.
The real story is more complex, and it is driven by the huge disappointments of the past two decades in psychiatric research, which have failed to lead to new drugs and have led to most large drug companies backing away from or abandoning the psychiatric field. Changing how patients with mental illness are diagnosed is going to take a lot longer than many people seem to think. The DSM is not being abandoned -- psychiatry is finally growing up.
I called the NIMH, and was put on the phone with Bruce Cuthbert, the director of the division of adult translational research. I had a pretty simple question. If the NIMH were really rejecting or abandoning the DSM, that would mean the agency wouldn't accept studies that use DSM-5 criteria. For instance, if you wanted to test a new schizophrenia drug in schizophrenics, you'd have to find some new RDoC way of describing the disease.
Cuthbert said repeatedly that would not be the case. It's not so much that studies that use the DSM-5 will be excluded and abandoned, but that researchers would now be allowed to apply for grants that would not use the manual's diagnostic criteria, or subdivided them in new, creative ways.
“Using DSM diagnoses for research has become a de facto standard ever since the DSM-III came out in 1980,” Cuthbert said. “What we are trying to do is to study neural systems directly because they cut across lots of the dsm disorders.” I asked the question again. “We are moving in a new direction. That doesn’t mean that next month we’ll stop accepting DSM diagnoses. It rather is a shift in emphasis.
New studies can still include DSM diagnoses, but their boundaries should not be limited by what's in the DSM. The new NIMH policy gives scientists the choice of going much broader, or being far more narrow.
In practice, grants at the NIMH are given out by a peer review scoring system in which anonymous experts critique proposals. At the end of the day, which grants get funded will depend on how they do in that system. So this change in focus will happen slowly, and will depend on the exact experiment being done.
The DSM-5 will still be the manual used by psychiatrists diagnosing patients, and it will still be used by insurance companies, and the government programs Medicare and Medicaid to decide what to pay doctors and hospitals for treating mentally ill patients. Cuthbert says that the NIMH is already working on ways to build “crosswalks” between the DSM-V and its new RdoC diagnosis system, which is still barely sketched out.
Why change at all? Cuthbert gives the example of one symptom of depression called anhedonia, the scientific name for inability to find pleasure in normally enjoyable activities. On the one hand, this condition occurs in lots of psychiatric illnesses, including anxiety and eating disorders. We don't know if it is neurologically similar in all of them or not. On the other hand, there are different types of anhedonia, Cuthbert says. Some people might go out to dinner with friends and not enjoy it. Others might be so down as to lack the energy to get to the restaurant in the first place, even though they would enjoy it once they arrived.
The NIMH's strategy with the RDoC approach is to dis-entangle a diagnosis like this. If there were a protein or blood test or brain scan that fit with one type of anhedonia (people with eating disorders who are too tired to go out for instance), but not with the others, it doesn't want to miss it. But this means taking the DSM-5 apart and re-assembling it through arduous experimental work. “It’s going to take a decade or more for results to bear fruit,” Cuthbert says.
The idea that psychiatry needs to become more focused on biological causes of disease, not associations of symptoms, is not new, either for Insel, who gave a TEDex talk on the topic, or to psychiatry as a whole. A recent paper in The Lancet, a medical journal, found that schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disorder all shared common genetic glitches as potential causes.
Behind all this talk about biology is a commercial reality: psychiatric drug development has become a dead-end. GlaxoSmithKline, Novartis, and AstraZeneca have stopped trying to invent new psychiatric drugs. Pfizer, Merck, and Sanofi have de-emphasized them. There are just 303 psychiatric drugs in development, compared to 3,436 cancer medicines and 1,247 drugs for other neurological disorders, according to the Analysis Group in a study commissioned by PhRMA, the drug industry trade group.
The introduction of the DSM-III in 1980 created a standardized language for psychiatry, and this did lead to big advances in psychiatric medicine. The next decade would see the introduction of anti-depressants like Prozac, Paxil and Wellbutrin and antipsychotic drugs like Zyprexa, Risperdal, and Abilify. In the 2000s, the NIMH funded big, independent clinical trials testing how well these medicines compared and how well to use them. A big study of the antidepressants found that a third of patients became symptom-free on taking them, but that switching those who were not helped to other drugs yielded diminishing results. A study of the schizophrenia drugs showed that, for just about all of them, patients and doctors chose to switch to another treatment three-quarters of the time, showing how difficult to use these medicines are.
But the strategy of conducting studies of existing drugs in thousands of patients fails when new drugs are not being invented. So Cuthbert says that the NIMH is very consciously focusing on small studies of new experimental drugs that drug companies have not embraced. The idea is to follow the “de-risking” model that has been successful for disease charities. The best example is Kalydeco, a drug for cystic fibrosis originally developed at Vertex Pharmaceuticals with funding from the Cystic Fibrosis Foundation. Eventually the drug became Vertex's most important product, demanding lots of resources and generating a high price. The idea is to try to get industry interested in psychiatry again. Changing the diagnostic system, seen as one reason that drugs are failing, is part of the job.
Jeffrey Lieberman, the chairman of psychiatry at Columbia University's College of Physicians and Surgeons, ran the NIMH's big schizophrenia trial. He is also a defender of the DSM in its current form. But he is also a big believer that psychiatry needs to base its decisions more on biology, and less on behavior.
“The DSM is the past and, for the time being, the present,” says Lieberman. “But it won’t be the future. The future it will be either improved or replaced by a more physiologically based set of diagnostic criteria. That may change the whole landscape for diagnosis.”
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cb1a74d1d37b917b0e158dad704ee915 | https://www.forbes.com/sites/matthewherper/2013/05/23/glaxo-alleges-errors-in-nissens-critique-of-fdas-handling-of-avandia/ | Glaxo Alleges Errors In Nissen's Critique Of FDA's Handling Of Avandia | Glaxo Alleges Errors In Nissen's Critique Of FDA's Handling Of Avandia
This morning, I published a guest post from Steven Nissen, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, alleging that the most likely rationale for an upcoming panel meeting being held by the Food and Drug Administration was to make some FDA leaders less accountable for the scandals that surrounded the diabetes drug Avandia. (See:The Hidden Agenda Behind The FDA’s Avandia Hearings.) This is the GlaxoSmithKline 's prepared statement in response to that article. The FDA's response can be found here.
Many inaccuracies exist in Dr. Nissen’s commentary and need to be addressed.
The RECORD study is the largest clinical trial designed to evaluate the cardiovascular safety of Avandia. The study conclusions have now been confirmed through a re-examination by one of the leading independent institutions in the country (Duke Clinical Research Institute). In the accepted hierarchy of evidence generation, the results of a randomized, controlled clinical trial usually take precedence over other forms of evidence such as meta-analysis and observational studies. Despite some limitations of trial design, including the open label nature of the study, RECORD remains the only randomized trial of cardiovascular outcomes for Avandia at this time. The confirmation of the RECORD results by the independent re-examination support a positive risk/benefit profile for Avandia for the treatment of type 2 diabetes in appropriate patients.
In contrast to Dr. Nissen’s allegations, GlaxoSmithKline, through its continuous and vigilant safety monitoring, identified a potential safety signal and proactively conducted a number of meta-analyses in 2005 and 2006 to evaluate the potential cardiovascular risk. The company kept FDA apprised each step along the way as we worked to evaluate our own meta-analysis, along with the other available data, and take appropriate action.
Dr. Nissen’s account of the Department of Justice plea agreement also differs from the facts. The plea agreement did not allege, and GSK did not admit that it had concealed cardiovascular safety information relating to Avandia. Rather, as part of a federal settlement, GSK admitted it did not include information about the initiation or status of certain Avandia studies in Periodic and Annual Reports submitted to the FDA. These inadvertent omissions from certain reports did not compromise the timely reporting of adverse events to the FDA from these studies, and as the FDA confirmed, did not change the FDA’s evaluation of the cardiovascular safety data for Avandia.
The upcoming FDA Advisory Committee meeting was not called at GSK’s request. The FDA’s long-established process – and the appropriate path for scientific engagement – is to gather a panel of external independent scientists to review data and make recommendations, ensuring independent judgment based on scientific expertise. During this meeting, the re-adjudication of RECORD, along with other data, will be presented.
I'm including Glaxo's entire statement here for the record, but I only saw one of these as an inaccuracy in the original piece: the description of the legal settlement. The others are differences of opinion, or facts that are in dispute.
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8ad6a00b260f821862d89c562191d3a1 | https://www.forbes.com/sites/matthewherper/2013/05/23/steven-nissen-the-hidden-agenda-behind-the-fdas-avandia-hearings/ | Steven Nissen: The Hidden Agenda Behind The FDA's New Avandia Hearings | Steven Nissen: The Hidden Agenda Behind The FDA's New Avandia Hearings
Steven E. Nissen
This post was written by Steven E. Nissen MD, the Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic. This commentary expresses his personal opinions and not necessarily the views of the Cleveland Clinic.
On June 5 and 6, the FDA will convene an advisory committee meeting on the diabetes drug Avandia, which was removed from the market in 2010 in most countries and placed under severe restrictions in the United States. Currently, only 3000 patients take what was once the best-selling oral diabetes treatment in the world. Its maker, GlaxoSmithkline (GSK), did not seek this public meeting and has publicly stated that it did not request modification to the drug’s extremely restrictive label. In 2012, GSK pled guilty to criminal misconduct related in part to concealing the hazards of Avandia and paid a $3 billion fine, one of the largest in U.S. history. In this context, why is the FDA seeking a new review of Avandia?
The most likely explanation: the leadership of the division of the FDA responsible for drug regulation, the Center for Drug Evaluation and Research (CDER), is seeking to avoid accountability for its role in the Avandia tragedy. In 2005 and 2006, GSK secretly conducted an analysis of the cardiovascular safety of Avandia and concluded that the drug increased the risk of heart attacks and related events by about 30%. This observation had grave implications: two thirds of diabetics, the intended recipients of the drug, eventually die of cardiovascular complications. Initially, GSK withheld the internal analysis from the FDA, but in 2006, the company informed CDER of the findings. FDA statisticians confirmed the risks, but, incredibly, CDER and GSK agreed privately to conceal this hazard from patients and practitioners.
In May 2007, my colleague Kathy Wolski and I published an independent analysis of Avandia in the New England Journal of Medicine (NEJM), showing a statistically significant 43% increase in heart attack. In Congressional testimony, CDER officials acknowledged that FDA statisticians had confirmed our findings, reporting a 40% increase in the risk of heart attack. The leadership of CDER was intensely embarrassed by these revelations and furious with us for publicly challenging the safety of Avandia (and indirectly the competence and integrity of CDER). The FDA appeared incredibly insensitive to the welfare of patients. GSK knew, FDA knew, but patients and physician were not warned.
Since 2006, CDER has expended considerable taxpayer dollars trying to absolve itself of responsibility for this inexplicable error in judgment that cost many lives. In 2010, CDER and GSK saw an opportunity clear Avandia of any cardiovascular hazard and scheduled an FDA Advisory Committee meeting to exonerate the drug. CDER had received the study report for a clinical trial known as RECORD, conducted by GSK in Europe to examine the long-term safety of Avandia. Because RECORD did not confirm a cardiovascular hazard, key senior CDER leaders saw this as an ideal opportunity to absolve themselves of culpability in the Avandia scandal. However, the CDER plan backfired during the public hearings for four reasons:
Independent FDA statisticians confirmed the hazards of Avandia, this time reporting an 80% increase in the risk of heart attack. FDA Deputy Commissioner Joshua Sharfstein took a personal interest in the issue and insisted that the Advisory Committee include independent scientists who would fairly judge the evidence. Dr. Sharfstein supported me in my request to present my independent analysis of the Avandia safety data to the committee. The RECORD trial was analyzed by legendary FDA reviewer, Dr. Tom Marciniak, a physician of the highest integrity and independence, and his review was devastating.
Marciniak’s 2010 review of RECORD showed extraordinary bias in the conduct of the trial. For example, the trial was unblinded; meaning that physicians and patients were aware which drug each patient was taking. Even GSK was unblinded. Incredibly, whenever a study site reported a clinical event, GSK and its contract research organization (CRO), knew immediately which drug the patient was receiving. Marciniak’s review showed that events occurring in Avandia patients were changed or deleted, sometimes months after they should have been reported and counted. These and many other flaws make the RECORD trial totally unreliable.
With a balanced committee membership and a fair hearing for both sides, the advisory committee voted overwhelming in favor of either removing Avandia from the market or severely restricting its usage (of 33 members, 12 voted for withdrawal and 10 for severe restrictions). European regulators banned Avandia entirely and US regulators relegated the drug to usage only in patients who had failed all other diabetes drugs.
However, the CDER leadership refused to accept the conclusion of regulators around the world and its own advisory committee that Avandia is hazardous. Instead, CDER arranged for the RECORD trial to be “re-adjudicated” (re-analyzed) by an outside group, the clinical trial center at Duke University. These Agency officials hope to show that the RECORD trial really did “prove” that Avandia is safe. If the RECORD trial was reliable, the logic goes, then the 2006 decision by CDER to conceal the risks of Avandia did not represent a dereliction of its public duty.
But GSK was allowed to prepare the materials for the Duke reanalysis, undermining the independence of the process. Beyond that, the entire idea of reanalyzing a trial that began in 2003 is simply ludicrous. Such a long interval seriously compromises the ability of adjudicators to retrieve original hospital records, laboratory findings, and other relevant patient data. Marciniak’s 2010 review revealed such extraordinary irregularities in the trial conduct that no subsequent effort could possibly correct the flaws.
The ostensible purpose of the June 5-6 Advisory Committee meeting is to consider the “re-adjudicated” RECORD trial. However, this time the meeting seems systematically designed to absolve the drug of harm and the CDER leadership of any responsibility for ignoring the public health hazard of Avandia. The current effort is intended to “whitewash” the Avandia scandal and re-write history. Certain respected and independent members of 2010 Advisory Committee have been recused from the 2013 meeting. I requested the opportunity to present an independent analysis to the Committee, but was denied and offered a 5-minute statement in the “open public hearing.”
Keen observers should compare the roster of this new committee to the 2010 hearings to determine which participants have been re-invited and which have not. Similarly, assess whether prominent drug safety experts within FDA, such as Dr. David Graham, are listed as speakers or excluded. Finally, will any GSK consultants address the panel?
Why are these hearings important? The FDA has been rocked by a series of scandals over the last decade. One FDA commissioner resigned under a cloud and later pled guilty to charges he had not reported owning stock in companies the agency regulated. Another commissioner resigned during the investigation of the use of political influence to gain approval of a medical device that was subsequently withdrawn. We have endured a series of drug and device safety disasters (Vioxx, Avandia, Ketek, defective defibrillator leads, and recently, compounding pharmacy oversight, and the list goes on) that have harmed many of our fellow citizens. In each case, the permanent FDA bureaucracy has sought to deny responsibility and often failed to learn the appropriate lessons necessary to prevent future catastrophes. In the middle of the sequester, CDER is willing to spend a large sum of taxpayer dollars to conduct a 2-day advisory meeting on a drug nobody uses, for the sole purpose of absolving its own bureaucracy of responsibility for a terrible drug safety tragedy. The current Director of CDER, Janet Woodcock, has directed this division for nearly 20 years, increasingly insulated from the Agency’s true constituency, the American public. If CDER is allowed to re-write the history of Avandia, this vital FDA Center will continue to function as an unsupervised, self-regulating bureaucracy, accountable to no one. That’s just unacceptable when the public health is at stake.
Dr. Nissen consults for many pharmaceutical companies, including companies making or developing diabetes drug. However, he requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction.
Update: The FDA says that Nissen was invited to the previous meeting because his analysis was relevant, but that the topics he is covering would be covered by other speakers. "The FDA encourages participation from all public stakeholders in the open public hearing portions of advisory committee meetings," the agency said. For the FDA's full comment, click here.
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790c70e4044777beaba028b79718253c | https://www.forbes.com/sites/matthewherper/2013/05/23/the-fda-responds-to-steve-nissens-criticism-of-upcoming-avandia-meeting/ | The FDA Responds To Steve Nissen's Criticism Of Upcoming Avandia Meeting | The FDA Responds To Steve Nissen's Criticism Of Upcoming Avandia Meeting
This morning, I published a guest post from Steven Nissen, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, alleging that the most likely rationale for an upcoming panel meeting being held by the Food and Drug Administration was to make some FDA leaders less accountable for the scandals that surrounded the diabetes drug Avandia. (See: The Hidden Agenda Behind The FDA's Avandia Hearings.) This is the FDA's response to that post, sent via its press office.
As part of the process of planning any advisory committee meeting, FDA staff consider the topic(s) to be addressed by the committee and make decisions about which review disciplines from the FDA should provide presentations to inform the committee discussion. FDA staff also determine whether non-FDA guest speakers should be invited to inform the committee discussion. Any guest speaker invited by the FDA must undergo screening for conflicts of interest. Every advisory committee meeting also includes at least a one hour opportunity for the public to present relevant information or views orally or in writing. This portion of an advisory committee meeting is known as the “open public hearing.”
In preparing for the July 2010 meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, the FDA sought to provide the committee members with all available data relevant to the cardiovascular safety of rosiglitazone. We were aware that Dr. Nissen had performed an update to the meta-analysis of rosiglitazone trials that he published in 2007, and the FDA considered it important to provide Dr. Nissen an opportunity to present these new data to the advisory committees. Therefore, Dr. Nissen was invited to present -- and did present -- his meta-analysis to the committees as an FDA guest speaker.
During the planning of the upcoming June 2013 AC meeting on rosiglitazone, Dr. Nissen contacted FDA staff and requested that he be invited as a guest speaker. To clarify the basis for his request, FDA staff asked Dr. Nissen to summarize what he proposed to present to the committees. Dr. Nissen indicated that he would summarize all of the available data on the CV safety of rosiglitazone; discuss the limitations of an attempt to readjudicate an old clinical trial; review any discrepancies between the adjudicated RECORD trial and the investigator-reported events; and discuss the public health implications of any decision to remove restrictions on the use of rosiglitazone.
FDA staff reviewed Dr. Nissen’s proposed topics and concluded they did not warrant a slot as an FDA guest speaker. The content of his proposed topics is expected to be covered by other speakers as agency staff plan to summarize the available data on the cardiovascular safety of rosiglitazone at the committee meeting, and multiple FDA speakers will address their review of the readjudication of RECORD trial based on the study reports submitted to the Agency.
FDA staff provided information to Dr. Nissen on how to request time to speak during the open public hearing portion of the meeting. Thus, Dr. Nissen was offered the same opportunity that is available to all members of the public interested in sharing their perspectives and opinions. It is our current understanding that Dr. Nissen has declined this opportunity.
The FDA encourages participation from all public stakeholders in the open public hearing portions of advisory committee meetings. We generally receive input from clinicians and researchers that represent professional societies, advocacy organizations, academic institutions and government agencies as well as patients and individuals who wish to share their perspectives on the topic being considered.
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afe20ff88bcc78b1b22a3dbf63618328 | https://www.forbes.com/sites/matthewherper/2013/07/14/the-best-and-worst-performing-biotech-stocks-july-5-to-july-12/?partner=yahootix | The Best- And Worst-Performing Biotech Stocks July 5 To July 12 | The Best- And Worst-Performing Biotech Stocks July 5 To July 12
These are the best and worst-performing medical and biotech stocks from July 5, 2013, to July 12, 2013. This screen includes biotechnology and medical companies traded on the New York Stock Exchange, the Nasdaq or the American Stock Exchange that had market capitalizations of more than $300 million as of a week ago. The data come from Interactive Data and Thomson Reuters Fundamentals via FactSet Research Systems.
The Best Performers
Recent 1-week 52-week Market price price value change change Ticker Company ($MIL) % % RNA Prosensa Holding N.V. 943.6 41.2 #N/A ALNY Alnylam Pharmaceuticals Inc. 3,111.0 32.3 302.6 ITMN InterMune Inc. 1,017.0 24.5 10.2 PCYC Pharmacyclics Inc. 7,865.2 24.2 98.3 EPZM Epizyme Inc. 993.3 22.0 #N/A TSRX Trius Therapeutics Inc. 473.5 19.4 67.9 ASTX Astex Pharmaceuticals Inc. 501.7 18.9 146.1 ACRX AcelRx Pharmaceuticals Inc. 455.4 18.9 256.6 VVUS VIVUS Inc. 1,479.8 18.7 -47.0 ALXN Alexion Pharmaceuticals Inc. 22,297.5 18.5 17.6
The Worst Performers
Recent 1-week 52-week Market price price value change change Ticker Company ($MIL) % % MACK Merrimack Pharmaceuticals Inc. 488.1 -27.4 -29.4 ISRG Intuitive Surgical Inc. 17,230.7 -14.9 -19.7 GTXI GTx Inc. 365.4 -14.6 57.5 BABY Natus Medical Inc. 370.4 -14.6 -3.2 AMRN Amarin Corp. PLC ADS 791.7 -11.7 -64.1 MDXG MiMedx Group Inc. 592.5 -6.9 180.9 CLDX Celldex Therapeutics Inc. 1,644.1 -4.4 291.7 ALOG Analogic Corp. 874.5 -4.4 15.8 FLDM Fluidigm Corp. 418.7 -4.1 23.7 NXTM NxStage Medical Inc. 823.8 -4.0 -11.6
The Best-Performing Biotech Stocks Of The Past 52 Weeks
Recent 1-week 52-week Market price price value change change Ticker Company ($MIL) % % SRPT Sarepta Therapeutics Inc 1,413.6 9.0 973.4 ACAD ACADIA Pharmaceuticals Inc. 1,463.8 2.5 944.6 AEGR Aegerion Pharmaceuticals Inc. 2,230.2 8.9 424.5 PBYI Puma Biotechnology Inc. 1,594.7 -0.3 394.3 ALNY Alnylam Pharmaceuticals Inc. 3,111.0 32.3 302.6 KERX Keryx Biopharmaceuticals Inc. 662.7 1.6 293.7 CLDX Celldex Therapeutics Inc. 1,644.1 -4.4 291.7 TEAR TearLab Corp. 343.6 7.2 260.5 ACRX AcelRx Pharmaceuticals Inc. 455.4 18.9 256.6 CLVS Clovis Oncology Inc. 2,208.7 -0.9 249.6 CYTK Cytokinetics Inc. 361.7 7.9 248.5
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9389f191462e96545ebbc226a43335ff | https://www.forbes.com/sites/matthewherper/2013/08/11/how-the-staggering-cost-of-inventing-new-drugs-is-shaping-the-future-of-medicine/ | The Cost Of Creating A New Drug Now $5 Billion, Pushing Big Pharma To Change | The Cost Of Creating A New Drug Now $5 Billion, Pushing Big Pharma To Change
Susan Desmond-Hellmann
There's one factor that, as much as anything else, determines how many medicines are invented, what diseases they treat, and, to an extent, what price patients must pay for them: the cost of inventing and developing a new drug, a cost driven by the uncomfortable fact than 95% of the experimental medicines that are studied in humans fail to be both effective and safe.
A new analysis conducted at Forbes puts grim numbers on these costs. A company hoping to get a single drug to market can expect to have spent $350 million before the medicine is available for sale. In part because so many drugs fail, large pharmaceutical companies that are working on dozens of drug projects at once spend $5 billion per new medicine.
Click here to see cost-per drug estimates for 98 companies over a decade.
“This is crazy. For sure it's not sustainable,” says Susan Desmond-Hellmann, the chancellor at UCSF and former head of development at industry legend Genentech, where she led the testing of cancer drugs like Herceptin and Avastin. “Increasingly, while no one knows quite what to do instead, any businessperson would look at this and say, 'You can’t make a business off this. This is not a good investment.' I say that knowing that this has been the engine of wonderful things.”
A 2012 article in Nature Reviews Drug Discovery says the number of drugs invented per billion dollars of R&D invested has been cut in half every nine years for half a century. Reversing this merciless trend has caught the attention of the U.S. government. Francis Collins, the director of the National Institutes of Health, in 2011 started a new National Center for Advancing Translational Sciences to remove the roadblocks that keep new drugs from reaching patients.
“One point your numbers tell you is how horrendous the failure rate is and how that causes the cost of success to be so much higher,” says Collins. “We would love to contribute to making that failure rate lower, to identifying those bottlenecks and to trying to reengineer the pipeline so if failures happen, they happen very early and not in later stages where the costs are higher.”
The good news is that a close look at the data we collected provides some hints as to how to improve the industry's hit rate – and how individual companies, without lowering the overall cost of developing a drug, can at least reduce their own expenses. Some companies – like Bristol-Myers Squibb, Regeneron Pharmaceuticals, and Aegerion – do far better than their peers.
Fighting The Law Of Averages
Where do my estimates come from? Using data from the Innothink Center for Research in Biomedical Innovation, I tabulated the number of brand new drugs launched by 98 publicly traded biotechnology and drug companies over the past decade. Then, using FactSet Systems, I tallied each company's research and development spending over the ten years preceding their most recent drug approval. Then I divided the second number by the first. (Again, the whole list and methodology is here.)
Sixty-six of the 98 companies studied launched only one drug this decade. The costs borne by these companies can be taken as a rough estimate of what it takes to develop a single drug. The median cost per drug for these singletons was $350 million. But for companies that approve more drugs, the cost per drug goes up – way up – until it hits $5.5 billion for companies that have brought to market between eight and 13 medicines over a decade.
Number of drugs approved R&D cost per drug ($MIL) Median Mean 8 to 13 5459 5998 4 to 6 5151 5052 2 to 3 1803 2303 1 351 953 Sources: Innothink Center For Research In Biomedical Innovation; FactSet Systems.
Why? For every small company that succeeds, there are many more that fail. A big pharmaceutical company carries that weight of failure, with both its successes and its failures on the books.
Why Does Big Pharma Spend So Much?
Some caveats, though: drug companies have tax incentives to count costs in research and development, which could inflate the figure; they also are likely to spend extra money in order to get those medicines approved in other countries. Even more important is the fact that some R&D costs come from monitoring the safety of medicines after they become hits to monitor reports of side effects. “Our safety infrastructure is close to 1,000 people,” says Paul Stoffels, the co-chairman of pharmaceuticals at Johnson & Johnson, which had the most new drugs approved and spent $5.2 billion per drug. “That is a whole biotech company and it is also part of our R&D budgets.”
Also, a small company cannot spend enough to pay for a $1 billion-plus program for a heart drug, as Pfizer, Roche, and J&J have, or for an Alzheimer's medicine. But if such a drug succeeds, the payoff can be enormous – see Pfizer's Lipitor, which is now generic but which had annual sales of $11 billion. Bigger drugs can be more expensive to develop.
10 Year R&D Spending ($MIL) R&D Spending Per Drug ($MIL) Median Mean >20,000 6348 6632 >5,000 2883 2961 >2,000 1917 2480 >1,000 1459 741 Sources: Innothink Center For Research In Biomedical Innovation; FactSet Systems
Size has a cost. The data support the idea that large companies may be spend more per drug than small ones. Companies that spent more than $20 billion in R&D over the decade spent $6.3 billion per new drug, compared to $2.8 billion for those that had budgets of between $5 billion and $10 billion. Some CEOs, notably Christopher Viehbacher at Sanofi, have faced low R&D productivity in part by cutting the budget. This may make sense in light of this data. But it is worth noting that the bigger firms brought twice as many drugs to market. It still could be that the difference between these two groups is due to smaller companies not bearing the full financial weight of the risk of failure.
Clear Winners
Among big pharmaceutical companies, there is a clear standout: Bristol-Myers, which under former research chief Elliott Sigal focused on understanding human genetics and using the immune system as a weapon against cancer. The result has been 9 drug approvals, including Yervoy for melanoma and Orencia for rheumatoid arthritis, at a per drug cost of just $3.4 billion, half that of Eli Lilly or Pfizer. “Look at what he accomplished,” says Desmond-Hellmann. “Holy cow.”
J&J, Novo-Nordisk, and Amgen also perform well, as do smaller companies like Regeneron, Gilead, and Biogen Idec.
One common mistake is allowing projects to linger on when the odds of success have become low, says Roger Perlmutter, who ran Amgen's R&D and is now doing the same thing at Merck. Another problem, he argues, is CEOs believing they can order up another drug like their last big hit, instead of following the science.
“Great drugs build great franchises, but great franchises don't necessarily build great drugs,” Perlmutter says. “If you are too prescriptive with your R&D, you can spend an awful lot of money and not be terribly productive because there may actually not be any new mechanisms that you can get to right now that will help you in a particular disease area.”
Another successful strategy is to focus on ultra-rare diseases; treatments for such ailments can cost $200,000 or more per patient per year, and be highly lucrative. But these drugs don't seem to eat up much in the way of R&D money. Genzyme, bought by Sanofi for $20 billion in 2011, spent $963 million per new drug. Alexion, the biggest stand-alone orphan drug maker,spent $490 million in R&D in the decade before its drug was approved; BioMarin, another orphan drug maker, spent just $134 million per drug.
The Power Of 'Who Pays?'
But reducing how much it costs to develop a new drug isn't the only way to reduce a company's cost. Another method: get somebody else to pay.
Many biotechnology companies benefit from deals in which a big pharma partner does some of the heavy lifting, for instance designing and running big clinical trials to prove a drug's worth. But small companies have also benefited by adopting drugs that were abandoned by the companies that invented them. Cubist Pharmaceuticals spent $220 million in R&D before its antibiotic, hit the market. But the drug, Cubicin, was invented at Eli Lilly, which put significant resources into developing it before abandoning it. Aegerion last year launched a new heart drug for patients with a rare genetic disease that causes super-high cholesterol; it had originally been developed by Bristol for heart patients, but abandoned because of side effects. Aegerion's R&D cost to get over the goal line? Just $74 million. The total cost spent on the medicine may have been triple that.
Philanthropies like the Michael J. Fox Foundation and the Multiple Myeloma Research Foundation now commonly use the strategy of bearing early research costs to get pharma interested. In the most visible example, the Cystic Fibrosis Foundation paid for the early development of a medication against that disease, a lethal lung ailment, at Vertex Pharmaceuticals. The result: a rare disease drug, Kalydeco, that is effective in patients whose CF is caused by a specific genetic mutation. Kalydeco costs $294,000 per patient per year.
The NIH is consciously imitating this approach. Collins, the NIH director, put former Merck scientist Christopher Austin in charge of his translational medicine institute and empowered him to fund further academic development of drugs that Big Pharma had abandoned, this time trying to find new uses for them. The idea is to improve the hit rate. Robert Beall, the CF Foundation's chief executive, warned them to think hard about whether they would try to limit the price of any drugs that result. Collins says that's impossible. “It's a non-starter,” says Collins. “Attaching government influence on the ultimate pricing is a way to kill the whole field.”
A Political Minefield
There is a long history of political controversy around drug industry claims about the expense of developing new medicines. Pharmaceutical companies have defended the prices of their drugs by pointing to past estimates of the cost of developing a new medicine. Most of these estimates, which took a bottom-up approach of estimating each step in the drug development process, came in far below the numbers I'm using here.
But this argument always had a sense of ridiculousness to it; it only works up to a point. A diamond might get more valuable if the path of transporting it to its eventual buyer were fraught with danger, but a lump of coal would not. At some point, drugs have to justify their own value. The cost of inventing medicines has become not a defense but an albatross; if costs don't come down, drug companies are in trouble.
Luckily, there are signs of hope. The Food and Drug Administration seems to be approving more drugs, even working with companies to help remove red tape and speed drugs for particularly serious diseases to market. And new technologies offer hope. Stem cells may allow for better safety testing of drugs, DNA sequencing for faster ways of figuring out what drugs to try to make. Collins, at the NIH, talks about developing organs in the lab that could be used for testing experimental medicines. Many companies are very consciously trying to remake and rejuvenate their R&D laboratories.
Then again, a lot of technologies have come and gone in the drug industry, often with the promise of lowering the cost of inventing a medicine. Yet the cost has gone up regardless.
“There are so many ways to fail that you always feel that you're ascending the steep part of the learning curve,” says Perlmutter. “You keep finding more and more ways of making mistakes that ultimately result in having to spend a lot of money and not getting products out.”
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bcbb1a744a448437309a5596ea45f75d | https://www.forbes.com/sites/matthewherper/2013/09/04/can-a-great-hospital-save-a-city/ | City Surgeon: Can The Cleveland Clinic Save Its Hometown? | City Surgeon: Can The Cleveland Clinic Save Its Hometown?
Delos M. "Toby" Cosgrove
Delos M. "Toby" Cosgrove arrived at the Cleveland Clinic in 1975 as an "incredibly poor" 34-year-old dreaming of a life as a cardiac surgeon. "Heart surgery was the astronaut corps of health care," he says. He had $3,000 in his bank account, left over from running an Air Force hospital in Vietnam, where he had won the Bronze Star. All his earthly belongings, including a Chevy Vega that was too flimsy to tow, fit in the back of a U-Haul.
During his first year someone was shot dead at the clinic's front door. The bank in the basement was robbed. To avoid crime, patients were told to take a shuttle bus the half-block back to the hotel where they stayed. The executive offices were all made with bulletproof glass. As the years passed he became well-known for pioneering the replacement of heart valves, eventually assuming the chair of the department of cardiothoracic surgery. Concurrently he created the clinic's office that oversaw the licensing of medical devices like surgical clamps and spine screws to companies like Medtronic and Boston Scientific. In 2003 he started looking for a second career, maybe as a venture capitalist in California, figuring that at 62 he was too old to operate. "I did not want to come to the end of my career and have someone saying, 'Toby, it's time for you to stop. You're getting a little shaky,' " says Cosgrove, now 73. Then he was offered the job as the clinic's chief executive.
The rough old neighborhood is a distant memory, replaced by a gleaming testament to modern medicine stretching out over 46 buildings and covering 167 acres. Protected by a dedicated 141-trooper force of state police, there is a conference center, a fancy hotel and a farmers' market. Over Cosgrove's tenure the clinic's revenues have nearly doubled to $6.2 billion.
Though the clinic is a nonprofit, its operating income sits comfortably between $250 million and $300 million each year. It has offices in Florida and will soon be operating in a giant steel-frame building in the Middle East in Abu Dhabi. The clinic has $10.5 billion in total assets. Forty-two thousand people--the equivalent of 11% of Cleveland's population--work there, making it Ohio's second-biggest employer, after Wal-Mart.
Four minutes down Euclid Avenue from the clinic is University Hospitals of Cleveland, a $2.3 billion facility also ranked among the nation's finest. University employs 19,000. A third hospital system, MetroHealth, employs another 6,200.
"The whole corridor between University Hospital and the clinic has regenerated. I barely recognize it," says Tom Gentile, chief executive of General Electric's GE Healthcare Systems unit. He lived in Cleveland in the early 1990s. "The clinic has attracted the best physicians in the world. It is a focal point."
But the city of Cleveland has fared less well. Its population has plummeted 17% to 396,816 between 2000 and 2010, and median income, already low at 66% of the national average, fell to 59.6% over the same period. Eighty-five percent of the city's income tax revenue now comes from people who live in the suburbs. Health care is the city's saving grace and a key factor in why Moody's Investors Service recently kept an A1 rating on the city's general obligation debt. "Health care has definitely been a stabilizing factor for them," says Moody's analyst Hetty Chang.
But stable is not good enough for Cosgrove. True to his venture capitalist ambitions, he's pushed to spin of f companies from the clinic--60 of them in the past decade. Together they have raised $700 million in outside equity funding and created 1,000 jobs. But it's nowhere near enough.
His brainstorm: a giant mall for hospital buyers. "Think about the things that go into a hospital. Shades, televisions, chairs, tables, wall coverings, all the medical gear, the operating tables, you name it," Cosgrove says. He envisioned a single building filled with futuristic showrooms where all of this stuff would be sold to doctors and hospital administrators. This, he hoped, would both lure big health care companies to the region and help jump-start Cleveland's convention business. County commissioners embraced the idea, and levied a cent sales tax to raise $465 million to create Cosgrove's medical market and a new, 767,000-square-foot convention center. The medical mart's grand opening is slated for October, and the convention center has already hosted its first event.
Not everyone is sold on the plan. Most convention centers throw off far less money than their promoters predict, and many cities wind up ?giving away space for free, says Heywood Sanders, an urban planner at the University of Texas at San Antonio who has studied Cleveland's strategy. "If your downtown doesn't function as a vibrant, interesting central core, what is going to make it interesting to visitors?" he wonders. "Is this a field in which it makes sense to compete? Is this something that plays to your natural advantages? Or is this something like the Rock and Roll Hall of Fame, a grand development gesture built more on hope than business sense?"
The Cleveland Clinic was founded in 1921 by George Washington Crile, a surgeon known for his work in treating shock, along with three doctors, two of whom he'd served with in the European theater in World War I. At the time, most doctors were--and 40% continue to be--independent businessmen who paid for space and operating time at local hospitals, but Crile was fascinated by the Mayo Clinic in Rochester, Minn., which paid its physicians a salary. The Cleveland Clinic imitated Mayo's system and also put docs on a yearly contract, making it far easier to let them go. The docs signed up for the relatively high pay and, more important, the opportunity to work with the best minds in their fields.
Salaried physicians have little incentive to order up extra procedures and tests because they don't get paid by the procedure, as most doctors do. And because they can lose their jobs, they stay on their game and work more closely with one another. "The clinic is special because it has been practicing a style of health care that is more collaborative and more evidence-based for literally a hundred years," says Bob Kocher, a health care investor at Venrock, the legendary venture capital firm started by Laurance Rockefeller.
Outside data back up the benefits: In the last two years of life Cedars-Sinai Medical Center in Los Angeles spends $146,165 per Medicare patient, according to the Dartmouth Atlas of Health Care. UCLA's Ronald Reagan Medical Center spends $137,248. The Cleveland Clinic? Just $86,279, even as it treats some of the sickest patients in the country. "We know the incentives of fee-for-service make it hard for physicians to do less because they'll lose income," says Elliott Fisher, director of Dartmouth's Institute for Health Policy & Clinical Practice.
"It's almost a patriotic obligation to begin to figure out how we do this," Cosgrove says, "because health care costs are going to eat education and all the social programs in the country if we can't control the costs going forward. We have to develop a new model for delivering care." He predicts that the Affordable Care Act, popularly known as ObamaCare, will be "a major step in disrupting the current system," forcing consolidation of hospitals that, if it is done right, will make health care in the rest of the country look more like Cleveland. Doctors will no longer be individuals but team players, employed by hospitals, just like in Cleveland.
Cosgrove first heard of the medical-mart idea in the late 1990s when he was spending a lot of time in Dubai. (Three thousand two hundred and ninety-five patients visited the clinic from other countries last year; 35% of them came from the Middle East.) But the notion really grabbed hold of him when his wife decided to remodel their house. She took him to the Merchandise Mart in Chicago, a 25-story building on two square city blocks run by the Kennedy family. It's filled with everything that you could need for a house: lamps, carpets, artwork, faucets, toilets. Other businesses orbited it, including antique stores, more furniture stores, design firms, even burglar-alarm companies. The whole thing made Cosgrove think that a Medical Mart could be the way to transform Cleveland, and he made it part of his pitch when he interviewed for the chief executive job.
Cosgrove had operated on John Cushman, who ran the real estate firm Cushman-Wakefield; through Cushman he was introduced to Christopher Kennedy (the son of Senator Robert F. Kennedy), who still managed Merchandise Mart Properties despite its sale to Vornado Realty Trust for $625 million in cash, stock and debt in 1998. In 2005 Kennedy and Cosgrove brought the med mart idea to Cleveland's mayor, who introduced them to his bosses, the county commissioners.
At the time, Cuyahoga County, of which Cleveland is part, was run by a committee of three equally powerful executives. They embraced the idea in part because it allowed them to attach the mart to building a new convention center, something they thought the city needed but which had proved politically unpopular. They selected Vornado's Merchandise Mart Properties to run the project.
The new plan proved unpopular, too. Then, in July 2008, the offices of one county commissioner, Jimmy Dimora, were raided by the feds in an anticorruption investigation. He was accused of accepting free meals, expensive liquor, sex with prostitutes, gambling junkets and home improvements from people seeking political favors, and was eventually convicted and sentenced to 28 years in prison.
In the wake of the Dimora scandal, a vote was held to completely overhaul the structure of the government, putting a single county executive in charge. In 2010 Edward FitzGerald, a JFK-esque Democrat who as an FBI agent had investigated relationships between the Mafia and local politicians in the Chicago suburbs, was elected to that job. It was unclear if the medical mart or the convention center would ever be built. "The facility had been designed and was starting the construction phase, there were virtually no tenants, and there was a real question about whether or not the business model itself was going to work," says FitzGerald. One problem immediately jumped out at him: Cosgrove, the Cleveland Clinic and University Hospitals had been locked out of the process. FitzGerald's first move: Call Toby.
Cosgrove called in an old friend, 30-year McKinsey veteran James Bennett. They'd raised their kids together, chatting about business at birthday parties and barbecues. Bennett, a silver-haired executive's executive, became a senior vice president at Merchandise Mart Properties, calling the work a civic service to a city he loves.
Bennett found that not only had the project lost touch with the Cleveland Clinic and University Hospitals but also with the companies that it was supposed to entice. He convened a committee, including top executives from Cardinal Health, Johnson & Johnson and Medtronic: What did they want? They started with the name, which is how Cosgrove's Medical Mart was transformed into the Global Center for Health Innovation. But they also wanted more than mere showrooms; they wanted flexible spaces that simulated things like operating rooms. And they wanted to help design them. Cosgrove got them involved--and turned them into likely tenants.
"We didn't have a space for demonstrations without taking customers to a working hospital, which is pretty disruptive and expensive," says Jim Dagley, a vice president at Johnson Controls, which outfits operating rooms with air ventilation and low-voltage electricity systems.
A stroke of luck came from another city's stumble. The Healthcare Information & Management Systems Society (HIMSS), a big industry trade group, had been planning to create a showcase for its work in Nashville, but the project fell through. Cosgrove got on the case. Says FitzGerald: "It's one thing for Merchandise Mart Properties or for a county executive to try to pitch this project to HIMSS, it's another thing for the CEO of the Cleveland Clinic to do it." The HIMSS Innovation Center now takes up 30,000 square feet of the Med Mart, the entire fourth floor.
What is emerging is an Epcot Center for med tech. GE Healthcare, Siemens, Philips Health Care and Cardinal Health are among the 22 confirmed tenants in the soon-to-be-completed center. Next door Bennett has already booked conventions that will bring 89,395 attendees this year and 100,400 next. By the end of 2016, he says, bookings should be enough to pay back the $465 million it took to construct both buildings.
It's understandable that Cleveland would bet so heavily on health care. As Kocher, the venture capitalist, puts it: "Playing off Cleveland's strength, which is the Clinic, makes a lot more sense than playing off another industry." But Sanders, the skeptic, says that may not be enough to beat the downward trends in the convention business. Attendance nationwide is shrinking or just barely up: According to Sanders' numbers, New York City's Javits Center had 1.3 million trade show visits in 2000 but only 533,700 in 2012; Orlando, Fla. doubled the size of its convention center but saw the number of attendees increase only 17% over the same period. Fitz?Gerald, now running for governor of Ohio, proudly points out the project came in $93 million below budget, and the unspent money will turn adjoining county offices into a hotel. Sanders questions the need: "Convention centers have been underperforming and failing from one end of the country to the other. They are doubling down on the bet."
Cosgrove is hoping for an economic spark. "It will begin to influence the city as it comes back and make it a destination medical city," he predicts. Still, any good surgeon will tell you it takes a while to see if an operation was successful. Cleveland isn't out of the woods just yet.
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b49f1874e3cec890e57786b0833f2c5a | https://www.forbes.com/sites/matthewherper/2013/12/26/the-most-important-new-drug-of-2013/ | The Most Important New Drug Of 2013 | The Most Important New Drug Of 2013
Gilead Sciences' Sovaldi, for hepatitis C, was the most important new medicine approved this year. It heralds the hope that a viral disease that afflicts more than 3 million Americans, can be treated with a few pills-- or even one – and that doctors and scientists may be able to dramatically reduce the toll of the infection, which can cause liver failure and death.
The benefit to society will only increase when Gilead launches a combination pill next year that, in clinical studies, result in sustained elimination of the virus in more than 9 out of 10 patients with the most common 'genotype 1' version of the disease. Analysts forecast Sovaldi will generate as much as $3 billion in annual sales in 2014, a new record for a drug launch, with sales going up from there.
Picking an winner was tough. Just as deserving of praise: Imbruvica, a treatment for mantle cell lymphoma, a rare cancer, developed by Pharmacyclics and Johnson & Johnson . In a 111-patient clinical study, 66% of patients saw their cancer shrink or disappear, an amazing result. (It's also being tested in other forms of blood cancer, and may be just as impressive.*) I gave the honor to Sovaldi because of the huge number of people it will impact.
The Food and Drug Administration has approved 27 new drugs, excluding new formulations or new uses for already approved medicines, so far in 2013. That's a 31% decrease from last year, but still marks a better-than-average haul for the pharmaceutical industry.
Here's what these two standouts can teach us about medical innovation:
There's lots of competition, with companies winding up on the same places on the Monopoly board. Last year, I gave the most important drug nod to Kalydeco, from Vertex Pharmaceuticals. That drug is dramatically effective in patients with the lung disease cystic fibrosis whose disease is caused by a specific mutation. That was a unique situation, because only Vertex and its partner, the Cystic Fibrosis Foundation , a charity, even thought about creating such a medicine.
That's not the case with this year's winner, or the runner up. Abbott Laboratories and partner Enanta have their own all-oral regimen for hepatitis C, but it requires patients to swallow six pills and one of those pills is ribavirin, a medicine that causes anemia and that many patients and doctors would rather do without. Bristol-Myers and Merck have also been pushing hard in the hepatitis C field.
Imbruvica also has competition – from Gilead. The company is developing another blood cancer drug, idelalisib, that seems nearly as effective. However, Gilead's cancer drug causes more serious diarrhea, which could weigh against it.
In pharma, inventors don't get as rich as investors. Both drugs demonstrate how the economic benefits of launching a new medicine can be far removed from the scientists and entrepreneurs who create them – drug inventors often don't get rich.
Gilead got Sovaldi when it acquired a small company called Pharmasset for $11 billion in 2011, which did result in a big payoff for the company's founders. But the biggest returns have come since, or are still to come. The deal also raises ethical questions about the way the drug was developed. In order to maximize its profits and, Gilead says, to speed development, Gilead dropped a collaboration Pharmasset had with Bristol-Myers Squibb. But the combo drug with Bristol worked better against one variety of hepatitis C, known as genotype 3, than the combo Gilead should launch next year, and some advocates think it was further ahead than Gilead's combo.
Imbruvica at one point belonged to Celera Genomics, when it was trying to be a pharmaceutical company. I'm not sure anyone knows who started developing the drug. It was bought by Pharmacyclics' previous chief executive before current boss Robert Duggan, an investor, took control. Since the ibrutinib results emerged, they have made Duggan a billionaire.
High prices are the rule. Both drugs are very expensive. Sovaldi costs $1,000 per pill, or $84,000 per course. Imbruvica costs $90 per pill, or $130,000 per year.
Other drugs that were big winners this year: Tecfidera, the multiple sclerosis pill from Biogen Idec; Gazvya, for chronic lymphocytic leukemia, from Roche, an heir to its best-seller Rituxan; Kadcyla, for breast cancer, also from Roche; and Pomalyst, from Celgene, for multiple myeloma.
*This sentence was added for clarity long after publication.
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3362894df435410818cf8fa9d997e545 | https://www.forbes.com/sites/matthewherper/2014/02/28/the-market-for-dna-sequncing-based-down-syndrome-tests-could-exceed-6-billion/ | The Market For DNA-Sequencing-Based Down Syndrome Tests Could Exceed $6 Billion | The Market For DNA-Sequencing-Based Down Syndrome Tests Could Exceed $6 Billion
On Wednesday night the New England Journal of Medicine published a study showing that a new, DNA-sequencing based blood test provides a dramatic improvement in accuracy at screening for Down syndrome and a second, deadly disorder. That could open up a $6 billion market to the biotechnology companies that are already marketing these tests.
Each year in the U.S. there are 6.6 million pregnancies and 4 million births, according the Centers for Disease Control & Prevention. The list prices of the tests, which are sold by four different companies, range from $700 to $2500. Assuming that pricing settles in the middle of that range and that there are 5 million women who choose to have the test, that would be a $8 billion market.
But give that number a haircut. “I have to imagine pricing could come down more aggressively if guidelines expanded,” says Douglas Schenkel, an analyst at Cowen & Co. Not every pregnant woman will ever get the test. But he still argues that the market for these tests could increase six-fold from its current size of about $1 billion. Isaac Ro, an analyst at Goldman Sachs, offered similar estimates in a note to clients.
Such a market expansion could be important to all of the companies that make the tests, including Ariosa, which makes the lowest price test, Natera, and Sequenom . But the biggest winner could be Illumina, the San Diego maker of DNA sequencing gear that funded the trial and that purchased Verinata, a fourth maker of the new tests, for $350 million last year.
Illumina says it believes Verinata has strong intellectual property position in this booming new market. Beyond that, though, all four manufacturers run their tests on Illumina's DNA sequencing machines, meaning the company wins no matter what. Francis DeSouza, Illumina's president, said in an interview that, if anything, he expects to spend less on marketing Verinata and that the company is taking care for there to be an even playing field for the tests. It prices its test in the mid-range of the market, at a $1,500 list price.
Illumina also says that it doesn't expect a price war, because the market expansion will be dependent on medical societies writing guidelines that endorse the new test. Right now the American College of Obstetricians and Gynecologists recommends the DNA-based tests only for mothers at high risk, including those over 35.
But the NEJM paper makes a strong argument for expanding that recommendation. Right now it's recommended that all pregnant women be offered a pair of tests – a blood test and an ultrasound to look for fluid at the base of the fetus' neck – to screen for three disorders caused when the baby has an extra copy of one of the 46 chromosome bundles that contain the human genetic code. There are three such disorders that occur commonly: trisomy 21, or Down syndrome, is the most common, causing diminished intellectual ability and slower growth; trisomies 18 and 13 are less common, but are often fatal for the infant.
Current screening tests yield a large number of false positives, so they must be followed up with an invasive test that samples cells from the fetus. One such test, chorionic villus sampling, has a miscarriage rate of 1 in 200; the other, amniocentesis, causes miscarriages 1 out of every 600 times.
These invasive tests would still be needed to confirm positives from the DNA tests, but they'd be used in women whose fetuses don't have Down or other trisomies far less often. The NEJM study gave the old screening tests and the new DNA-based test to 1,914 pregnant women and followed them until the baby was born. For Down Syndrome, the new test gave just 6 false positives compared to 69 for the old screening tests. For trisomy 13, there were 3 false positives with DNA sequencing compared to 11 with the traditional number. For trisomy 13, the numbers were 1 and 6.
Assuming 5 million women are tested each year, that would mean 245,000 would be spared an invasive test, and 358 miscarriages might be prevented. Even at a higher cost, that could be hard for insurance companies to say no to. Some experts, including Illumina, expect that more studies will be needed to change the guidelines.
How does the new test work? Basically, by counting. Because some of the fetus' cells circulate in the mother's blood, researchers can sequence DNA and see if genes from any chromosomes appear too often. For a more complete description, check out the video embedded from Steve Quake at Stanford, who co-invented Verinata's technology. His explanation starts at 5:55.
Not everyone is sure that the new technology, known as non-invasive prenatal testing, is an unmixed blessing. Hank Greely, a professor of law at Stanford Law School who has written extensively on genetic issues, says that the new test is “more reason to think NIPT will largely take over Down screening.” But he warns that these same methods might lead to tests for more complicated tests. “If, say, 70% of American pregnancies received broad genetic screening, the next generation would look different - some will say for better, some for worse.”
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93d2e4760a272e259c2565b17b8a475d | https://www.forbes.com/sites/matthewherper/2014/04/16/a-lucky-drug-made-pharmacyclics-robert-duggan-a-billionaire-will-long-term-success-follow/ | A Lucky Drug Made Pharmacyclics' Robert Duggan A Billionaire. Will Long-Term Success Follow? | A Lucky Drug Made Pharmacyclics' Robert Duggan A Billionaire. Will Long-Term Success Follow?
Robert Duggan was enjoying just your average Tampa vacation--a visit to the headquarters of the Church of Scientology, to which he's a major donor, and a double date with one of the world's top supermodels--when a board member at Pharmacyclics , a biotechnology company he had invested in, interrupted the party with some urgent news. The board was resigning en masse in favor of his slate of directors. Duggan, who had run a cookie company and pioneered startups in Ethernet and robotic surgery--but knew zilch about running a biotech firm--would take the helm.
That was in 2008. Six years later, improbably, Duggan is a billionaire. Duggan had made the investment in large part because of personal passion. Since his son had died from a brain cancer, "I knew more about brain tumors than the average guy walking down the street, because we had to look for support in handling his condition." But the brain cancer drug Xcytrin never made it to market. Duggan has nonetheless made Pharmacyclics work, buying shares when no one else would, funding it with $50 million of his own money and riding it all the way up.
There's always a good deal of luck involved in biotech. In Duggan's case, he had a sleeper in the pipeline: Imbruvica, which turned out to be a potent treatment for chronic lymphocytic leukemia, shrinking tumors in 58% of patients failed by all other drugs, and mantle cell lymphoma, a rarer disease. Johnson & Johnson inked a $975 million deal to copromote Imbruvica in 2011, beating out other Big Pharmas, and Pharmacyclics' stock has risen fortyfold since that fateful phone call, turning his stake into a $1.4 billion fortune.
Now Duggan says that he plans to use Imbruvica as the basis for creating a new successful drug company. Pharmacyclics already boasts 500 employees, and he says its other ?experimental drugs have promise, too. "This is the time to be in the business," he says. "You build a company up, and you have resources and an engine of capacity to execute, because of its vision, leadership and execution."
He talks of "the body harmonious," his idea that the body can be made to fix itself, and of "patient-friendly" medicine, a sense cemented at his robotic surgery company, Computer Motion, sold for $68 million in 2003, that treatments can be made safer--for instance, by using robots to do heart surgery.
It's a wonderful vision. But can a manager with no experience hunting for drugs build a drug company? Second acts in the biotech business are hard: 56% of the drug firms that received an FDA approval between 1950 and 2011 did so only once.
His track record for drug development is hardly convincing. When Duggan started buying up Pharmacyclics shares, his goal was to build Xcytrin, not bury it. In a 2008 tender offer, he said his goal was to "use all available means to encourage and to urge Pharmacyclics to pursue another trial." Pharmacyclics' then chief executive and founder, Richard Miller, had taken up the strategy of trying to shame the FDA into approving Xcytrin, a plan that was unlikely to work and was causing Pharmacyclics shares to sink.
But internally Miller's attention was already turning to Imbruvica, which he had bought from Celera Genomics, the company known as one of the first to sequence the human genome, for only $6.6 million in 2006 as part of a three-compound deal. He hired Celera scientists who understood the drug and says he was designing the first clinical trial to test the drug himself. When Duggan recommended a new slate of directors, Miller says, his board, fearing a proxy fight they couldn't win, made the call to Duggan and resigned. One board member tried to broach a reconciliation, but Miller says he wouldn't have returned, and Duggan says he wouldn't take him. Both men are bitter, but Miller is still an Imbruvica fan. "I actually think it could be the biggest-selling oncology drug," Miller says.
Once in command Duggan charged a nine-person committee with advising him on how to proceed with Xcytrin. The vote came back 9-0 that Xcytrin was done. Duggan still believes Xcytrin would have succeeded if Miller had run the right trials. It hardly matters. In December 2010 data showing how potent Imbruvica was were announced at a blood cancer meeting. Pharmacyclics' shares soared.
Now Wall Street is falling out of love. Pharmacyclics' shares are down 12% year-to-date, falling behind the iShares Nasdaq Biotechnology Index, which is down 2%. Duggan's efforts to build a medical team have hit bumps. For instance, he hired industry veteran Lori Kunkel to head drug development, calling her a "genius," but she left 19 months later, saying she'd done what she had set out to do by getting Imbruvica approved.
Investors have been unimpressed with prescriptions of Imbruvica so far, even though the drug looks likely to beat sell-side forecasts. Geoffrey Porges, an analyst at Sanford C. Bernstein with a record of picking the top for biotech stocks, has been cautioning investors on the stock. One problem: Another lymphoma drug, from Gilead, looks very similar. Jacqueline Barrientos, a professor at North Shore-Long Island Jewish hospital who worked on clinical trials of both drugs, says that their efficacy is similar, though Gilead's pill causes more diarrhea.
Kunkel, for one, has faith in Duggan. He "brought the company up to a different level," she says, adding that "Bob is a very ?astute businessman." And Imbruvica is a breakthrough drug and still has blockbuster potential--if it weathers further FDA approvals and extends patients' lives, increasing the size of its own market. But to get there it will take time, work--and more than a little luck. That's the thing about the drug business: Overnight success often means you're just getting started.
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d8ff0930cad8ad8d87026dc342ed45d3 | https://www.forbes.com/sites/matthewherper/2014/10/25/a-defense-of-the-ebola-quarantine/ | A Defense Of The Ebola Quarantine | A Defense Of The Ebola Quarantine
When Andrew Cuomo and Chris Christie, the governors of New York and New Jersey, announced that they would be putting in place an enforced quarantine when medical workers who had contact with Ebola in Liberia, Sierra Leone, or Guinea enter the United States, my immediate reaction was that this was a bad decision. The reason: it would make it practically impossible to for doctors to volunteer to go to those places and risk their lives to try to help end the epidemic. That they reportedly didn't even consult their health commissioners made me feel worse.
I wasn't the only one who thought that, of course. Arthur Caplan, the NYU Langone Medical Center bioethicist, wrote a piece suggesting that if we're going to lock docs up, it should at least be in a nice hotel with wine and Wi-Fi. And Paul Offit, chief of the division of infectious diseases at Children's Hospital of Philadelphia, wrote in an email to me:
If someone is afebrile and asymptomatic, they aren't contagious. The New York city doctor acted in a responsible manner. The minute he noticed his first symptom (temperature of 100.3 degrees) he quarantined himself. The people who are at risk of catching Ebola in the United States are ICU workers taking care of patients who are vomiting and have diarrhea, bodily fluids which contain large amounts of virus. The Dallas patient was intubated and dialyzed, two procedures that put those taking care of him at risk. His fiancee, on the other hand, who was with him earlier in his illness, never caught the virus, even though she likely kissed him and slept with him.
But not everyone agrees. I also contacted Pascal J. Imperato, the Dean at SUNY Downstate Medical Center and former New York City Health Commissioner. He surprised me with the strength of his response. His basic response to the idea that fewer volunteers will be going to Africa is to say that maybe volunteers aren't that effective anyway, and that their lack of actual experience may make them more likely to catch Ebola. Imperato writes:
I strongly support the decision by New York and New Jersey to quarantine those entering these states who have been exposed to those with active Ebola disease infections in Africa. This especially applies to volunteer US health care workers who have been providing health care to Ebola patients in Liberia, Guinea, and Sierra Leone. As demonstrated by the case of Dr. Craig Spencer, self-monitoring simply does not work. The New York and New Jersey quarantine regulations are timely since they address the next phase in the control and prevention of this epidemic, and that is the responsible management of returning medical volunteers and others with a history of close contact with Ebola patients. I would add that while the willingness of such volunteers to go to West Africa is admirable, good intentions are no substitute for competent practice and experience in caring for Ebola patients. Most American medical volunteers working in the epidemic zone are there short-term, their pre-departure preparation excellent to uneven, and their previous experience in treating patients with a highly communicable and deadly disease often non-existent. The Centers for Disease Control and Prevention has hesitated to implement the quarantine regulations now in force in New York and New Jersey out of a concern that they will discourage medical volunteers from going to the epidemic zone in West Africa. However, such a position is based on an unproven assumption that these volunteers are vital to the treatment of Ebola patients. This assumption has not yet been supported by firm evidence. A revolving door of short term and quickly trained American volunteers leaves many understandably uncomfortable since they are often trained, but not practice experienced. It is the latter that is crucial in preventing care givers from acquiring this infection in a therapeutic setting.
Those are strong words. But if we can't send volunteers, because they won't learn infection control procedures fast enough, what do we do? The thing that most increases the odds of Ebola coming here is for the epidemic in West Africa to become larger. It doesn't matter how hard you try to stop up the drain, if you keep pouring water in, it's going to leak or burst. Are we just forced to hope the epidemic burns itself out, or to wait for vaccines to be developed by GlaxoSmithKline, Johnson & Johnson, Inovio, or Newlink? We just sit and wait as things get worse? That seems...that is terrible.
We do need to make sure that one Ebola case here does not turn into many, or, God forbid, to allow the virus to take up residence here. But it does seem, from both Imperato's previous comments to me and Offit's, that the risk of infection for Americans remains vanishingly low. Probably 1,000 people died of methicillin resistant staphylococcus aureus in our hospitals since Ebola first showed up in the U.S. It's true that Ebola could become a much bigger problem. It's an infectious disease, and it can spread. But I worry that our panic is both not addressing the core problems that make us bad at infection control and distracting us from actually figuring out ways to deal with this problem.
I don't know how to feel on the quarantine, which, I suppose leaves me in the position of acceding reluctantly to its existence. But I do hope that we've got better solutions than travel bans and quarantines, because these don't fill me with confidence.
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5833dacb7136dae1ddaaceddaea6f6f2 | https://www.forbes.com/sites/matthewherper/2014/11/03/rothberg-returns-with-star-trek-like-medical-device-to-create-images-and-cut-with-sound-waves/ | Rothberg Returns With Star Trek-Like Medical Device To Create Images And Cut With Sound Waves | Rothberg Returns With Star Trek-Like Medical Device To Create Images And Cut With Sound Waves
When we last left Jonathan Rothberg, the entrepreneur who first throttled DNA sequencing onto its Moore’s Law-beating path, he was leaving behind his genetics work in the tangle of Thermo Fisher’s $14 billion purchase of Life Technologies , which had previously bought his startup, Ion Torrent.
Rothberg, one of the most colorful entrepreneurs in biotech, went strangely quiet for eighteen months. Now he’s back with a new incubator (called 4Combinator) and a new startup, Butterfly Network, into which he has put $20 million of his own money and $80 million more from investors to develop a device that sounds like it’s right out of Star Trek: an ultrasound scanner that can give vivid images quickly and cheaply, and that will eventually be able to use beams of concentrated sound to perform some types of surgical procedures.
It’s one of three companies – including a drug company and another started to create tools for physicists – that Rothberg is building.
“If you’re a great programmer and a great deep learning expert, you don’t have to help Netflix pick the best movie for the client,” says Rothberg. “You can help people pick the right cancer drug.”
The Butterfly Network ultrasound device, like much of Rothberg’s work, sprung from his interest in tuberosclerosis, a genetic disease that afflicts 50,000 Americans and causes benign tumors in the heart, kidney, skin, lungs, eyes and brain, where seizures can occur. Rothberg’s oldest daughter suffers from it, and he has run a charitable institute that funds research into the disorder.
Rothberg had been impressed by doctors who used ultrasound to not only image tumors in the kidneys of some patients with TSC, but also to break them apart. The problem: getting the images took days and at least $2 million worth of equipment, and placing the ultrasound beams was incredibly difficult.
A kidney imaged with Butterfly's technology.
Then he attended a conference where he saw Max Tegmark, the MIT physicist, speak about how if radioastronomy would be completely different if it were completed from scratch using Moore’s Law-era technology. Rothberg was fascinated, and approached Tegmark afterward and told him he couldn’t come up with a business plan to use Tegmark’s techniques in astronomy, but he saw a way forward in medicine.
“The bottleneck for me is not money, it’s not opportunity, it’s having the first person on the team,” says Rothberg.
Tegmark had that first person, an MIT electrical engineer who had triple-majored in math, physics, and engineering who had always wanted to start a company. That researcher, Nevada Sanchez, became the co-founder of Butterfly. Rothberg says that the imaging device may be available in just 18 months, although the ability to use the device to target tumors with ultrasound will take longer.
It’s a big leap, both in that it’s a new technology and in that Rothberg, who has until now focused on starting one company at a time, is now doing three with the goal of starting more. Ion Torrent failed to succeed in unseating the main player in DNA sequencing, Illumina of San Diego, because its technology did not improve fast enough and because Life Technologies, which bought the company, overpriced the machines. Will Rothberg be able to do better on his own?
“The hurdles are really in the execution and in the marketplace,” says Greg Rehm of Aegis Capital, who is backing Butterfly. “Because of its performance and price points you’ll be disrupting the clinical marketplace, and that’s always a risky undertaking. We think the benefits are so great the company will be able to overcome that.”
Rothberg will also be speaking at the Forbes Healthcare Summit on December 4.
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8024ce6518ffec57e597407984c16c2f | https://www.forbes.com/sites/matthewherper/2014/11/17/after-years-under-attack-mercks-vytorin-proves-effective/ | After Years Under Attack, Merck's Vytorin Proves Effective | After Years Under Attack, Merck's Vytorin Proves Effective
Since 2007, the blockbuster cholesterol pills Zetia and Vytorin have been under a cloud as many doctors questioned their effectiveness at preventing heart attacks – and those questions have caused prescriptions of the pills to fall by more than 50%. Today, that cloud lifts.
An 18,000-patient trial shows that Vytorin, which combines Zetia and the older drug simvastatin, prevented more heart attacks, strokes, and other heart problems than simvastatin alone, exonerating the drugs. Merck revealed that the study succeeded in a press release this morning.
Image credit: Schering-Plough via Getty Images
The release reads, in full:
Merck (NYSE: MRK), known as MSD outside the United States and Canada, today said that IMPROVE-IT met its primary endpoint. The results are scheduled to be presented at the American Heart Association Scientific Sessions later today. The data are embargoed by the American Heart Association until the start of the late-breaking clinical trials session at 10:45 a.m. CT today.
I’ve seen the full results, but, under an agreement between reporters and the AHA, I can’t reveal them until the embargo lifts.
But just knowing that the study succeeded is enough to say the following: this is good for Merck. It means that the company will avoid yet another controversy about its past behavior and ethics. It also could mean a bump in sales.
The result is good for the drug industry as a whole. The backlash against Vytorin was part of a distrust of drug companies that started with another Merck medicine, the painkiller Vioxx, which caused heart attacks and was withdrawn from the market. It was driven by things that Merck and Schering-Plough did: trying to avoid bad data, marketing both medicines to too broad a population, faking meeting minutes and paying doctors large sums to talk up drugs. And it poisoned the industry’s relationship with consumers and the FDA.
That will benefit other companies developing cholesterol drugs, because it could mean faster approvals of those medicines by the Food and Drug Administration and more rapid sales uptake when and if the the medicines hit the market.
Investors should expect the stocks of Amgen, Regeneron, Sanofi, and Esperion to most directly benefit from this news.
At the heart of the Vytorin story is a big scientific question: how much can we trust that lowering the bad cholesterol, known as low-density lipoprotein, or LDL, means preventing heart attacks. This study won’t completely settle this issue, but it does mean that scientists and doctors will assume that cutting LDL means preventing heart attacks and strokes.
Also on Forbes:
Gallery: Global 2000: The Biggest Drug Companies Of 2014 10 images View gallery
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1b7030f105f87c8e5c26837d1a168eb2 | https://www.forbes.com/sites/matthewherper/2014/12/19/juno-shares-exploded-post-ipo-should-you-consider-buying-them/ | Juno Shares Exploded Post-IPO. Should You Consider Buying Them? | Juno Shares Exploded Post-IPO. Should You Consider Buying Them?
One of the most exciting companies in biotech just had one of the year’s most exciting initial public offerings.
Shares of Seattle-based Juno Therapeutics increased 60% from their listing price to $38 in late morning trading in the biggest biotech IPO of the year. The company will have a total market capitalization of $2.85 billion. Juno is raising $265 million from the offering, which will add to the $300 million war chest that Juno raised in private offerings.
When it began its roadshow, Juno was expecting to sell shares at $16 to $18. The much higher price is a sign of the excitement around the technology that Juno is developing: what are known as chimeric antigen receptor T-cells, or CARTs, genetically modified versions of a patient’s own white blood cells that have been trained to kill cancer.
Investors (as well as scientists and doctors) are exhilarated because these cells have the ability to do amazing things in patients with blood cancer who have failed other treatments. Patients like Milton Wright, who I met while reporting a cover story on CARTs earlier this year. At age 17, he’d gone through two previous bouts of acute lymphoblastic lymphoma. He was modeling for The Gap and playing football when the disease came back. His own T-cells were removed, genetically modified using a virus, put back into him, and within a few weeks the cancer was gone.
But he also got fevers from the treatment, which can be much, much worse for some patients. This is called cytokine release syndrome, and it’s a serious side effect for CART treatments. Across various trials presented at the recent American Society of Hematology meeting, Juno CARTs resulted in complete remissions of between 60% and 90% of patients treated, depending on the disease. But researchers also saw cases of cytokine release syndrome, including one death, and neurological problems, including delirium. Not every patient who gets a complete remission remains cancer free.
Juno is not alone in the CART field. Novartis seems to have an early lead. Kite Therapeutics, which has a market capitalization of $2 billion, is targeting B cell lymphomas, an area where Juno and Novartis aren’t as far ahead. Celgene and Bluebird are collaborating on CARTs, and smaller companies, like Bellicum and Cellectis, are also in contention with technologies like CARTs with off switches, so they won’t keep working indefinitely, and off-the shelf CARTs that don’t need to be made from a patient’s own cells.
It’s early days for this field. As Stan Riddell of the Fred Hutchinson Cancer Research Center, one of Juno’s co-founders, told me earlier this year: “There have been more articles in the lay press about patients treated with CART cells than there have in the scientific press. We're talking about a handful of patients. Now what we need is really rigorous clinical trials that address the questions of how CART cells work and what the side effects are and that data.”
That’s the challenge for all the CART companies, but don’t expect it to happen slowly. Novartis, Juno, and KITE all say they expect to file for approval with the Food and Drug Administration to sell the CARTs for very sick patients in 2016. (Novartis started first, spent $43 million on a plant built by the now-defunct cell therapy company Dendreon, and seems to be likely to reach patients first.)
So what advantages does Juno have to warrant a valuation that is 50% greater than Kite’s? Well, for one thing, a lot of cash. But the other is that it is a company created from more of the scientific leaders in this field than any of its competitors. Novartis’ entire effort is based on the CART technology developed by Carl June at the University of Pennsylvania. Kite’s comes from immunotherapy pioneer Steve Rosenberg at the National Cancer Institute.
Juno is instead based on three separate programs: one based at Memorial Sloan-Kettering in New York, a second from the Fred Hutch, and a third (related to the Hutch work) from Seattle Children’s. The idea is that by being connected to a whole network of laboratory researchers and that by developing similar CART programs in parallel, Juno will have a scientific edge over other CART developers in creating cells that have fewer side effects and better efficacy.
Right now, though, it’s hard to know whether that will pan out. It’s also more difficult and expensive to manage more programs at once. Those are all questions investors should think about before buying Juno shares.
A few more big questions we don’t have answers to: How much will CART therapy cost? In some cases, it is replacing bone marrow transplants that cost $350,000 per patient, and this has been proffered as a potential cost for the treatment. But some CART patients still go on to have bone marrow transplant anyway. Novartis Chief Executive Joseph Jimenez has told me that figure is far too high as a price.
And what about intellectual property? The situation with CART cells appears to be very different from that with drugs, where often a single patent will allow a company to maintain a monopoly. There’s a lot of overlapping intellectual property, but most sources I speak to have trouble imagining a judge ordering an injunction on a lifesaving treatment. These are likely to result in some CART companies paying royalties to others, but the main question is how they can develop the safest, most effective treatments and deal with the high manufacturing and distribution costs inherent in this kind of treatment. It’s in these areas that Juno’s expertise should prove an advantage.
Another thing worth mentioning: right after an IPO pop may not be the best time to buy. Even in the fast-paced world of CARTs, there's going to be time to figure out exactly how good an investment Juno is.
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96ebf7d029f8dad02801bbd9ef9a3a41 | https://www.forbes.com/sites/matthewherper/2014/12/29/why-less-is-more-getting-better-outcomes-from-simpler-medication-regimens-for-complex-patients/ | Why Less is More: Getting Better Outcomes from Simpler Medication Regimens for Complex Patients | Why Less is More: Getting Better Outcomes from Simpler Medication Regimens for Complex Patients
A large body of research shows that a young and healthy adult’s working memory has the capacity to store between three and five “chunks” of information. Think about how you recall a phone number; most people use three chunks. Thus, it is not at all surprising that medication adherence is a notable problem; especially for the 20% of Americans asked to take five or more prescription drugs every day. More scrutiny, and perhaps even forced prioritization to limit medications below a certain threshold (e.g., no more than five), is needed in prescribing guidelines for individuals on multiple medications.
If the upper bound of working memory is five chunks for someone that is healthy and relatively young, how can we expect someone that is sick, and in many cases, experiencing age-related cognitive decline, to remember an even greater amount of information and instructions?
For example, take the unfortunately all too common case of a 67-year-old man with diabetes, hypertension, high cholesterol, chronic pain, and mild-depression who has been prescribed six drugs to manage his conditions. Three of the drugs should be taken once a day, two should be taken twice day, and one should be taken every other day. Four are to be taken with meals while two are to be taken on an empty stomach. Drugs one and five should never be taken together, unlike drugs two and three, which are most effective when paired. It is hard enough to count the chunks of working memory needed for this man, let alone to remember both to take the medications and the instructions.
Layered on top of this extraordinary memory challenge is the fact that many lack motivation to take their medications in the first place. This occurs for many reasons ranging from not feeling better after taking a medication, to a lack of knowledge for why a medication may be necessary, to unpleasant side effects, to the feeling of lost autonomy, to the medications serving as a constant (and unpleasant) reminder that the person is sick. Consequently, it doesn’t take behavioral a scientist to recognize how unreasonable it is to expect adherence out of individuals taking five or more medications. Yet we continue to do so, even amidst studies that show that as the age and number of drugs that someone has been prescribed increase, so too does non-adherence, to rates exceeding 50%.
It would be one thing if non-adherence occurred in a predictable and linear fashion where people forgot to take (or improperly took) the least important drug(s). Unfortunately, non-adherence is not neatly ordered like this. The relatively small marginal benefit that a patient obtains by taking drug number seven may come at the grave cost of forgetting to take, or improperly taking, a far more important drug. Not to mention, additional drugs increase the risk of adverse interactions and subsequent consequences, most notably falls in older populations.
While an emerging suite of new apps and other technologies is attempting to solve the problem of medication non-adherence (and will undoubtedly help), the best first-line defense is prioritizing the drugs prescribed to begin with. This will require one clinician to be responsible for compiling all of a patient’s prescriptions (from across all of their doctors), understanding the rationale and clinical goals for each medication, understanding a patient’s goals, and then logically rationalizing what combination makes sense. This is particularly difficult given the complexity of a medication regimen is non-linear. Increased scrutiny in prescribing behavior should not only take into account adverse side-effects and interactions, but also the cognitive costs for a patient of needing to remember to take an additional medication. The marginal benefit of the “next” drug should always be weighed against the increased risk of a patient forgetting to take or improperly taking far more critical ones.
Addressing medication non-adherence will be particularly challenging in today’s hyper-specialized medical system, where physicians often “own” a single organ system or disease and thus are likely to overweigh the net benefits of any single drug that affects that respective organ system. Overcoming this challenge will require taking a more holistic look at the costs, benefits, and risks (both physical and cognitive) of multiple medications for patients.
Much like most clinical-decision support systems currently flag potential drug interactions at the point of prescribing, they could also flag whenever a patient is taking five or more medications, and require the prescribing physician to document a rationale (i.e., over-ride) explaining why the benefits of the “next” drug outweigh the added risks of global non-adherence. Software advances are rapidly making it possible to quantify (for an individual patient) the specific benefits of unique medications and combinations of medications, as well as the side effect risks and costs.
In addition, an increasing role for pharmacists to consult on and/or co-manage patients taking multiple medications would be beneficial since in many cases, only the pharmacist knows all of a patient’s medications. (Electronic health records often do not integrate seamlessly and primary care physicians may be unaware of other doctors a patient is seeing.) This is likely to become even more complicated as an increasing number of patients take advantage of convenient services like video-telemedicine, retail clinics, and urgent care centers.
An approach where clinicians are forced to think of a patient’s capacity to be adherent with medications as limited by human memory, as well as a patient’s ability to manage complexity, is a concept that should guide clinician prescribing decisions. Much of the “blame” for non-adherence likely falls on physicians who, without thinking, or knowledge of a patient’s entire regimen, prescribe medications that lead to schedules that would be too complicated for even the healthiest young-adults to remember and comply with. If we considered a limit of no more than five medications per person - and forced each incremental medication to have a compelling rationale - we would likely end up with better outcomes as patients would at least have a possibility of being fully compliant.
Bob Kocher is a venture capitalist at Venrock focusing on healthcare IT, and a Consulting Professor at Stanford University School of Medicine, and Former Special Assistant to the President for Healthcare and Economic Policy. Brad Stulberg works in population health for a large and integrated health care system and is also a health writer where his work appears in media outlets ranging from the LA Times to Men’s Fitness. Authors' opinions are their own.
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4e822e4010e8176cde0c2858a7beb22c | https://www.forbes.com/sites/matthewherper/2015/01/05/30-under-30-the-entrepreneurs-making-healthcare-digital/ | 30 Under 30: The Entrepreneurs Making Healthcare Digital | 30 Under 30: The Entrepreneurs Making Healthcare Digital
Gallery: 2015 30 Under 30: Healthcare 31 images View gallery
Our annual list of the best-and-brightest in healthcare and science was so dense that we decided it was time for a spin-out.
This year there are two lists: this one, for entrepreneurs who are changing the healthcare space, and a second for pure scientists, which you can find here.
The 30 Under 30 in Healthcare focuses on a long list of founders, along with a few economists, policy wonks, and researchers, who are finally dragging our medical system kicking and screaming into the digital age.
Take Nat Turner, 28. He and his co-founder, Zach Weinberg, began working together on internet startups after they met while walking across campus at Wharton. Their first was a food-ordering company focused on campuses (think Seamless for undergrads). Then they started an Internet advertising company, Invite Media, that they sold to Google for a reported $81 million. But “Zach and I’s heart wasn’t in advertising,” Turner tells us.
Instead, he’s dealing with saving and collecting all the vital healthcare data lost in handwritten charts and bad electronic medical record systems. The idea is to use machine learning to capture this information. Flatiron charges doctors to use the system, but the real big revenue will come from selling what Flatiron learns to drug companies and health insurers.
David He, an MIT grad and co-founder of Quanttus ($22 million raised from investors including Khosla Ventures and Matrix Partners), has found that small, imperceptible movements can be used to measure heart health – potentially allowing for a new generation of wearables. Katelyn Gleason, 29, is chief executive of Eligible API, which checks whether patients are insured automatically, instead of forcing a doctor to make a phone calle. Investors including Esther Dyson have put in $1.5 million. TJ Parker’s PillPack is a new kind of pharmacy that sends pills in individual packs to help make sure patients remember to take them. It has collected $12.85 million in funding from Accel Partners, Atlas Ventures, and others.
Then there are the big thinkers. MIT Assistant Prof. Nikhil Agarwal is using economics theory to understand how the medical match, which decides where doctors train, works. Maria Pereira, 29, has developed a new adhesive that might be used to patch holes in a beating heart.
Perhaps most inspiring is David Fajgenbaum, 29, a University of Pennsylvania professor who has developed a global research network to attack multicentric Castleman Disease, a rare disorder of the lymph nodes. When chemo failed, he had his last rites read to him, but he returned to med school and is now fighting back with research.
For more on the list, click through the gallery above or find the entire list here.
Special thanks go to the judges for this project: Bob Kocher, a partner at Venrock; Jonathan Rothberg, chief strategy officer of 4Catalyzer, a new incubator that is on the lookout for young talent, and Christi Shaw, US country head and president, Novartis Corporation.
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d2a9cb2e8e43572d63325ee45e1abeff | https://www.forbes.com/sites/matthewherper/2015/01/06/surprise-with-60-million-genentech-deal-23andme-has-a-business-plan/ | Surprise! With $60 Million Genentech Deal, 23andMe Has A Business Plan | Surprise! With $60 Million Genentech Deal, 23andMe Has A Business Plan
This is more like it.
A deal being announced today with Genentech points the way for 23andMe, the personal genetics company backed by Facebook billionaire Yuri Milner and Google Ventures to become a sustainable business – even if the company’s discussions with the U.S. Food and Drug Administration stretch on for years.
According to sources close to the deal, 23andMe is receiving an upfront payment from Genentech of $10 million, with further milestones of as much as $50 million. The deal is the first of ten 23andMe says it has signed with large pharmaceutical and biotech companies.
Such deals, which make use of the database created by customers who have bought 23andMe’s DNA test kits and donated their genetic and health data for research, could be a far more significant opportunity than 23andMe’s primary business of selling the DNA kits to consumers. Since it was founded in 2006, 23andMe has collected data from 800,000 customers and it sells its tests for $99 each. That means this single deal with one large drug company could generate almost as much revenue as doubling 23andMe’s customer base.
“I think that this illustrates how pharma companies are interested in the fact that we have a massive amount of information,” says Anne Wojcicki, 23andMe’s chief executive and co-founder. “We have a very engaged consumer population, and these people want to participate in research. And we can do things much faster and more efficiently than any other research means in the world.”
Alex Schuth, who heads technology innovation and diagnostics business development at Genentech, says he was drawn by the 12,000 patients 23andMe has recruited with the help of the Michael J. Fox Foundation, and by the physical data on those patients. “That is something unparalleled,” he says. “Obviously the goal for us for this collaboration is target discovery to find new medicines for patients in a disease-modifying sort of way.”
The deal comes at a critical time for 23andMe because in late 2013 the Food and Drug Administration told the company it could no longer return health information to its customers. This has hurt sales. It also makes it difficult for 23andMe to build its database and make it more appealing to large pharmaceutical companies.
The Genentech deal is not the first one with a drug company that 23andMe has done – it has had collaborations with pharmaceutical companies going back to the company’s founding. Last year it announced a collaboration with Pfizer to enroll more than 10,000 patients with colitis or Crohn’s disease in its database to look for genetic clues to the cause of those bowel disorders.
But the new deal shows the scale and power of 23andMe’s existing database (or, as 23andMe refers to it, community) in a way that others have not. Genentech, the U.S. unit of Swiss drug giant Roche, will make use of one of the biggest communities on 23andMe’s website: the one for Parkinson’s.
Wojcicki and her husband Sergey Brin (the two are now separated) have been very public about their desire to understand Parkinson’s, which runs in Brin’s family. 23andMe has signed up 12,000 Parkinson’s patients and 1,300 of their parents and siblings. These participants are amazingly willing to volunteer for research. In one study, one of 23andMe’s partners wanted to take a deep skin biopsy from 24 patients in 23andMe’s database who had a particular Parkinson’s mutation. Eight patients volunteered within 24 hours.
23andMe’s tests only scan the genome for known variations. Genentech wants to go deeper, and will pay to get full genome sequences – that’s all of a person’s DNA – for 3,000 Parkinson’s patients or their first-degree relatives. The goal, Schuth says, is to discover new targets for drugs and diagnostic tests. The companies have not yet decided who they will hire to do this DNA sequencing.
People who have bought 23andMe kits and agreed to donate their data to research (that’s about 600,000 of the company’s 800,000 customers) automatically consent for 23andMe to sequence their genomes. 23andMe says that it is also able to share anonymous and pooled data about their self-reported health traits without asking. But Genentech wants even more: it wants to look at health and genetic data on an anonymous but individual basis. For that reason, the company will have to ask customers if they want to enter the study.
One big question behind 23andMe’s business model has always been whether customers will be happy or upset when they find out that they realize they have paid to be used in for-profit research projects. “I’m sure some people will feel great, no problem, and some will feel cheated,” says Hank Greely, director of the Center for Law and the Biosciences at Stanford University. “And the reactions will form a bell curve.”
But Greely says those issues are unlikely to apply to this deal. The fact that 23andMe will be getting consent from participants makes things a lot cleaner. So does doing the study in Parkinson’s patients and their relatives, who have engaged with 23andMe partly for the purpose of doing disease research.
“When we've had people come in who have a disease, they are very clear that they want us to do whatever it is going to take to actually make a difference in their disease,” says Wojcicki. “They're just very, very clear about that. Do whatever it takes that's going to have an impact on my life or an impact on the lives of my children.”
One big question is when 23andMe will once again be allowed to let consumers in the United States access data about their health. The legality of 23andMe’s product has been a thorny question since the company was founded in 2006. Even at its peak, 23andMe could not analyze tests sent from the state of New York because of the laws there. (New York residents could send their 23andMe kits in from somewhere else.)
In 2012, 23andMe announced that it had raised $50 million in funding from investors including Google Ventures, Facebook billionaire Yuri Milner, and New Enterprise Associates. Wojcicki said that the company planned to grow its customer base to 1 million, significantly expanding its ability to do research. 23andMe began to run advertisements that emphasized the health benefits some customers had gotten from its tests.
At the same time, 23andMe was supposed to be trying to work with the FDA to figure out how to clear its test as a medical device. But in November 2013 the FDA sent 23andMe a scathing, public letter, saying that the company had been radio silent with regulators for six months and telling it to stop giving health information or risk an enforcement action. I said at the time that 23andMe might have “the single dumbest regulatory strategy I have seen in 13 years of covering the Food and Drug Administration.”
Wojcicki ticks off a number of steps that 23andMe has made to fix its relationship with the FDA. She hired Kathy Hibbs, from Genomic Health, a maker of cancer diagnostics, to manage the company’s relationship with the regulator. And 23andMe has been in constant dialogue with the FDA since submitting an application last May.
“I am hopeful for 2015,” Wojcicki says. “It has been quite a transformation for the company, to really change and go through this entire process.”
There is really no telling, though, how long it will take to get the consumer business on track and to get FDA approval. If the database of genetic and health information 23andMe has built were not already valuable, the company would be facing a dicey future.
But if Genentech is willing to pay for access to the data, it may well be valuable enough now. There are other indications that 23andMe, while not as big as Wojcicki dreamed, is big enough to matter. One analysis using patient-reported data predicted asthma as a side effect for Genentech's cancer drug Herceptin. An analysis presented at the American Society for Human Genetics last year said that genes related to drugs that had been successful were present in 23andMe’s database. Reset Therapeutics, a small South San Francisco biotech, is using 23andMe’s database to hunt for rare disease drugs.
Eventually, 23andMe will need to start growing its genetic database again, and doing that will require reigniting the consumer business. But it can afford to wait. Wojcicki says that she has always been playing a long game.
When she first started 23andMe, she says, someone at a Big Pharma company told her that if she really wanted to make a difference in the world, she would be ready to work for 10 years with the FDA to define what direct-to-consumer genetic testing would look like as a business. If not, if she wanted to sell the company quickly, she’d need a totally different strategy.
“At 23andMe, we made that choice then,” Wojcicki says. “We are very much in it for the long haul.”
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def33965020c2bf9e82daaa70d518384 | https://www.forbes.com/sites/matthewherper/2015/01/12/roche-spends-1-03-billion-for-majority-stake-in-cancer-genomics-firm/ | Roche Spends $1.03 Billion For Majority Stake In Foundation Medicine | Roche Spends $1.03 Billion For Majority Stake In Foundation Medicine
Roche, the world's largest maker of cancer drugs, is spending $1.03 billion to buy a 56.3% stake in Cambridge, Mass.-based Foundation Medicine, a company that uses genetics to help select drugs for cancer patients. Roche, based in Basel, Switzerland, will also market Foundation's diagnostic tests outside the U.S., help educate doctors as to the value of the tests in the U.S., and provide another $150 million to support additional research on Foundation's products.
Roche is buying 15.6 million Foundation shares at $50 each, about twice the current stock price, on the open market and will purchase another 5 million newly issued shares from Foundation at $50 per share. In a setup that echoes the one that Roche had for years with Genentech, the biotechnology company it later bought, Foundation will continue to function as an independent company. Despite its majority stake, Roche will have only 3 of 9 seats on Foundation's board. "We both feel it’s important for Foundation to maintain its independenence and its entrepreneurial spirit," says Michael Pellini, Foundation's chief executive.
This is a big deal for Foundation and for use the genetic tests in cancer care. Foundation has had some big-time support -- investments from Bill Gates and Google Ventures, partnerships with Novartis and Celgene -- but this deal is likely to increase use of the tests both in medicine and in drug research. Even though there has been a biotech boom of late, Foundation has had trouble capturing investors' imaginations. Foundation Medicine shares are down 32% since the company's IPO in 2013, compared to a 20% gain for the S&P. One big concern has been that it will be difficult to get insurers and Medicare to pay for the technology; the other is that there may be lots of competition, including from hospitals that just buy an Illumina DNA sequencer and run cancer gene panels themselves.
Roche's investment is certainly not proof that everything for Foundation is going to be OK. The company has run DNA sequencing technologies into the ground (see 454 Life Sciences, once a leader, now a footnote). Fifteen years ago, many big drug companies bought into early genomics pioneer companies and got nothing in return. But it certainly helps that Roche is willing to pay double the value of Foundation's shares.
I'm not going to launch into a long analysis of who will win in the cancer genetics space, or of Foundation's position, this morning. Instead, I'm going to leave you with the story of a Foundation Medicine patients whose lung cancer was put on pause, at least temporarily, as a result of the company's test. The video below, from a young woman named Corey Wood at the Forbes Healthcare Summit in December, shows how important Foundation and its competitors could be. "Sometimes, the job, and the journey, chooses you, and in some ways I'm not that bitter about it."
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6216e627907199775da5a6d957a2e53b | https://www.forbes.com/sites/matthewherper/2015/01/15/lawsuit-says-billionaires-health-venture-is-fraudulent-and-could-harm-patients/ | Whistleblower Lawsuit Calls Billionaire Patrick Soon-Shiong's Healthcare Startup 'Fraudulent' And Dangerous | Whistleblower Lawsuit Calls Billionaire Patrick Soon-Shiong's Healthcare Startup 'Fraudulent' And Dangerous
On the television newsmagazine “60 Minutes” and in a cover story for Forbes, Patrick Soon-Shiong, the world’s richest doctor, has promised that his new company, NantHealth, can dramatically improve care for cancer patients everywhere. “I’m incredibly encouraged to say that we are on the path,” Soon-Shiong told 60 Minutes’ Sanjay Gupta. “And the technology to actually do all these things is not just hypothetical.” He told me: “My quest was and is to improve the quality of life through science.”
But a lawsuit filed yesterday in Panama City, Fla., where some of the operations of NantHealth are based, alleges that the company is anything but a dramatic leap forward. Instead, two former employees say that NantHealth is “engaged in a multitude of fraudulent activities” and broke laws related to health privacy and billing. The former employees say NantHealth and its parent, NantWorks, ignored their warnings “of the potential harm their products were exposing their patients to.” (Read the lawsuit here.)
The claims in the lawsuit raise doubts about a planned initial public offering of NantHealth, which has collaborations with cell phone maker Blackberry, which is providing hardware for its next generation devices, and biotech giant Celgene , which is using the company’s technology to study experimental drugs.
The plaintiffs had senior roles at Nant. Stephanie Davidson was hired last August as NantHealth’s Senior Vice President, Professional Services. William Lynch was hired last March and was promoted on August 4 to head NantHealth’s marketing as the Senior Director of Marketing. They both relocated to Panama City, a Metro Area in the Florida panhandle with a population of 170,000. The two lived together and were in a relationship.
“This lawsuit was filed after Nant turned down a demand by Ms. Davidson and her boyfriend Mr. Lynch for $2 million with an accompanying threat that unless Nant paid, Ms. Davidson and Mr. Lynch would launch a smear campaign filled with false and damaging information,” said Steve Curd, NantHealth’s Chief Operating Officer, who says he terminated both plaintiffs for “improper behavior.” He adds: “The facts are the allegations are false.”
Nant’s software and hardware are intended to link together different hospital devices in ways that current electronic medical records like those made by Epic Systems of Verona, Wisc., and Cerner , of Kansas City, Mo., can’t. In this way, every device connected to a patient, from a heart monitor to an insulin pump, would automatically collect data in real time. But the suit says that when Davidson arrived, she found that the technology violated privacy requirements put in place by the Health Insurance Portability and Accountability Act of 1996 and wasn’t up to Food and Drug Administration regulations.
Moreover, she says, Nant’s customers were rebelling. The suit claims the chief information officer of Piedmont Healthcare was threatening to stop working with Nant and to warn other hospitals not to upgrade either. She says 14 other customers were about to “throw out” Nant’s product. She also says an internal report commissioned by Soon-Shiong found that Nant’s Clinical Operating System (cOS), “as a platform, is ten years behind in technology capability. It is not ready for large enterprise use, much less for cloud deployment.” The report found the system was unreliable and “runs on LUCK.”
Davidson also alleges that NantHealth and Soon-Shiong’s charitable foundation may have worked to defraud the government. She says that NantHealth was using money from the Centers for Medicare and Medicaid Services (CMS) “in an unlawful and fraudulent manner. The suit alleges that, as an example, Soon-Shiong’s charitable foundation might donate $10 million to a joint venture between NantHealth and Phoenix Children’s Hospital, which would then use the money to obtain matching funds from CMS of $30 million. Then the joint venture would purchase products and services from NantHealth, essentially making the government pay for Nant products and getting additional funds, too.
Lynch alleges that Nant made misleading claims in marketing materials including “true patient engagement,” interoperability, security, safety, ongoing viability of its system for tracking patient vital signs, and the functionality of genetic and protein-based cancer tests. The suit alleges that many customers were incurring huge costs as a result of NantHealth’s products not working properly.
Davidson and Lynch claim they were fired after she told Laura Beggrow, NantHealth’s executive vice president, commercialization, that she was worried that misrepresenting the capabilities of the company’s products might harm Soon-Shiong’s reputation. They are suing under a Florida law that prohibits employers from firing employees for reporting violations of laws or regulations to superiors or authorities.
Curd, the NantHealth COO, points out that Davidson was employed for less than 3 months and Lynch for less than 9. “When Ms. Davidson was fired she reached out to the CEO requesting that he reverse the COO's decision to terminate her saying, ‘I love what we are doing and believe in the company’,” he says. “When this reversal was denied her lawyer sent repeated requests for a $2 million payment to avoid a smear campaign. Nant denied the payment request and the couple filed this baseless lawsuit filled with inaccuracies and false statements.” A call to the lawyer representing Davidson and Lynch was not returned.
NantHealth lawsuit by Matthew Herper
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a6a99222c15ef7a94356bd911802f592 | https://www.forbes.com/sites/matthewherper/2015/02/11/neuroscience-treatments-to-watch/ | Neuroscience Treatments To Watch | Neuroscience Treatments To Watch
This article is a companion piece to Brain Boom: The Drug Companies Bringing Neuroscience Back From The Brink. Breakthroughs in genetics and sheer stubbornness on the part of drug developers could soon lead to new drugs for intractable brain diseases. Here's a look at what's happening in five different areas:
DEPRESSION
Outlook: Very good. Fast-acting drugs are already in late-stage trials after showing great promise.
Currently: Existing drugs take weeks to have an effect.
What's next: Faster-acting drugs. Alkermes is testing one that is in late-stage trials that works in days, not weeks. A J&J inhaled derivative of ketamine and new drugs being developed by Naurex all seem to work in minutes on depression that doesn't respond to other drugs.
Long term: Eli Lilly has a new antidepressant pill that has shown some promise. Johnson & Johnson and Lundbeck are studying how depression might be the result of misfires by the immune system that damage the brain.
MULTIPLE SCLEROSIS
Outlook: Very good. Drugs may even reverse the disease.
Current: Multiple sclerosis has been the neurological disease with the most advances for patients because doctors were able to discover its root cause--an overactive immune system--and focus treatments there.
What's next: More pills along the lines of Biogen Idec's Tecfidera and Novartis' Gilenya, which keep the immune system from damaging nerves, are in development, including Forward Pharma's FP187.
Long term: The big thing to watch is whether any drug can reverse the damage the immune system does and help nerve cells regrow. One candidate is Biogen Idec's drug known as anti-LINGO, which should show some results next year.
PARKINSON'S DISEASE
Outlook: Advances coming soon, but big breakthroughs may take years.
Currently: The disease, which causes shaking and loss of coordination, is treated with a synthetic drug, levodopa, that boosts levels of the brain transmitter dopamine.
What's next: Many therapies focus on what to do when levodopa wears off. Acorda Therapeutics is developing an inhaled version. Voyager Therapeutics is testing a gene therapy that may make levodopa effective again when patients have developed resistance.
Long term: Attempts by Merck, Roche and Pfizer to block a genetic mutation that can lead to Parkinson's ran into problems when drugs caused lung damage in monkeys. Biogen Idec hopes to clear toxins that build in the brain as a result of the disease.
SCHIZOPHRENIA
Outlook: Fair. Interesting drugs in development but not enough of them.
Currently: Drugs can be effective at treating hallucinations and paranoia but don't yet treat cognitive problems and social difficulties caused by the disease.
What's next: Add-on drugs. In 2016 Forum Pharmaceuticals hopes to have results on its encenicline, aimed at helping schizophrenics think more clearly. Acadia Pharmaceuticals is testing its Nuplazid to help existing antipsychotics.
Long term: Intra-Cellular Therapies, a new publicly traded company, is testing a pill that, instead of working outside neurons, gets deep inside them. "It could be the most promising advance in antipsychotic pharmacology [in decades]," says Jeffrey Lieberman, psychiatrist in chief at NewYork-Presbyterian Hospital-Columbia University Medical Center.
ALZHEIMER'S DISEASE
Outlook: Treatments that have a big impact are unlikely anytime soon.
Currently: Industry bet big on injectable medicines to prevent or reverse Alzheimer's by attacking the buildup of plaques in the brain--and failed.
What's next: A lower-risk approach: targeting Alzheimer's symptoms but not trying to reverse the disease. Forum Pharmaceuticals expects results from one such drug next year. Another drug from Lundbeck is in late-stage trials.
Long term: Drug companies won't give up on the plaque approach. Biogen Idec presents data for its plaque-buster in April; Eli Lilly could release results of a big retrial of a failed drug next year; Roche is testing a plaque-buster in patients with a gene that causes Alzheimer's before age 40. Merck, J&J and others are testing plaque-clearing pills.
Go back to Brain Boom: The Drug Companies Bringing Neuroscience Back From The Brink.
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eda07b2951a4bb16d6b45944b558fdb4 | https://www.forbes.com/sites/matthewherper/2015/03/31/what-i-hope-everyone-learns-from-pbs-big-cancer-documentary/ | What I Hope Everyone Learns From PBS' Big Cancer Documentary | What I Hope Everyone Learns From PBS' Big Cancer Documentary
No surprise: PBS’ “Cancer: The Emperor of All Maladies” is exactly the documentary one wishes every person who has ever been captivated by a breathless news report about cancer research would watch first. No surprise, because the book, by oncologist and researcher Siddhartha Mukherjee, was exactly the same thing in written form.
It’s a pity both are so long – the book is a doorstop, and the documentary series takes six hours to watch. But here’s a quick insight, from the first two-hour chunk that aired last night, that I wish everyone remembered every time they get news about cancer, including when they read my stories.
Siddhartha Mukherjee, left, and Ken Burns speak on stage during the "Cancer The Emperor Of All... [+] Maladies" panel at the PBS 2015 Winter TCA on Monday, Jan. 19, 2015, in Pasadena, Calif. (Photo by Richard Shotwell/Invision/AP)
There have always been magic bullets. And they’ve never been quite magic enough.
That goes for aminopterin, the Lederle drug that, in the hands of the legendary Sidney Farber, produced the first remission in children with leukemia in 1947. The documentary gets across how pyrrhic that victory was by interviewing a man who, as a small boy, watched his twin brother, who’d responded to the aminopterin, carted away by men in an ambulance for the last time.
And it goes for the brilliant and terrible 1965 realization by National Cancer Institute oncologists Emil Freireich and Emil Frei that giving four toxic drugs at once was the way to treat childhood leukemia. It worked, saving at first a third of patients. The strategy was so toxic at first that Farber would never embrace it.
Built into these advances is an inevitable cycle of hope (as we first realize we’re making progress) and disappointment (as we realize that new treatments have their own costs and that none are perfect). Over time, the progress is real, and amazing: today, childhood leukemia is curable 90% of the time.
Having this simple story in the back of your mind is maybe the most useful fact you can have when looking at new advances, like Novartis ’ Gleevec, which has turned a form of adult leukemia into a chronic disease, or the drug Imbruvica, which led to a 75% reduction in mortality in patients with chronic lymphocytic leukemia; its maker was recently bought by AbbVie in a $21 billion deal.
And it is eerie to think about the similarities between what happened with childhood leukemia in the 60s and what is happening now: a new treatment for the 10% of kids who fail combination chemotherapy involves taking out their white blood cells, genetically modifying them, and re-injecting them so they bloom and kill off the cancer cells. Results so far are amazing, and companies including Novartis, Juno Therapeutics, and Kite Pharma are all talking about moving beyond blood cancer to solid tumors like breast and lung cancer. Will this turn out to be as difficult as it has been with Freireich and Frei’s insight about chemotherapy? Will it take forty years?
“To imagine that we will find a simple solution to this, I think, doesn’t do service to the true complexity of the problem,” Mukherjee says in the documentary. “Cancer is part of our genetic inheritance. We will always have cancer amidst us, within us, amongst us.”
There are four more hours of cancer film to go, airing tonight and tomorrow night.
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011b19fe363915dd32dde9348b20a39a | https://www.forbes.com/sites/matthewherper/2015/05/07/how-fake-news-articles-and-lies-about-billionaires-were-used-to-market-an-iffy-dietary-supplement/ | How Fake News Articles And Lies About Billionaires Were Used To Market An Iffy Dietary Supplement | How Fake News Articles And Lies About Billionaires Were Used To Market An Iffy Dietary Supplement
You’d be forgiven for thinking it was a Forbes story about a revolutionary new product. After all, the Forbes logo was there, Forbes was in the URL – ForbesMemoryPlus dot com – and the punchy writing described a breakthrough pill used by billionaires. Not just any billionaires, either: Berkshire Hathaway’s Warren Buffett, Microsoft’s Bill Gates, and internet billionaire and “Shark Tank” celebrity Mark Cuban. There’s also a clipped article from Forbes magazine, supposedly bylined by former Forbes scribe Robert Langreth, alongside the cover of our issue on The World's Billionaires.
Except the whole thing is made up. Forbes had nothing to do with the site, Langreth never penned the article, and the billionaires have never heard of this miracle pill, a dietary supplement called BrainStorm Elite. “The only brain-enhancing potion I take is Cherry Coke,” quips Buffett. Cuban says he doesn’t take the pills, but that if he did, they are “obviously not working.”
The whole operation traces to a shady web site – which apparently ceased operation when it received inquiries from Forbes – selling a supplement whose impact on mental acuity is iffy at best. Promotional material for BrainStorm Elite included forged articles and screencaps from a host of media properties, including CNN, Scientific American, Discover Magazine, and ABC News. The company that makes the supplements disavowed ownership of these advertisements, saying that they were produced by “affiliate marketers” who were not its responsibility. In fact, many of the websites investigated by Forbes traced back to a single individual whose phone voice mail said he worked at a carpet cleaning business. One of the product's pages -- BrainStormElite.org, but not BrainStormElite.com -- is registered to a self-styled new age internet entrepreneur.
“That’s something that we typically see,” says Richard Cleland, assistant director in the Division of Advertising Practices at the Federal Trade Commission. “A lot of fingerpointing. ‘I’m not to blame, they’re to blame, I didn’t get the money, they got the money, I didn’t write the ad, they wrote the ad.’ I think from our point of view it’s not a legal defense. We can and have and will go after the manufacturer and the affiliates.”
The FTC, however, had never heard of BrainStorm Elite before I called them, and had no plans to prosecute.
What this is is the blending of two lightly regulated and murky industries: dietary supplements and internet marketing. The first has long been able to make medical claims without the kind of regulatory review that medicines go through. The second can use networks of individuals to create web pages, sometimes posted as advertisements on sites like Facebook or Yahoo, whose sole purpose is to route consumers to other pages that actually sell the product. The result is well-designed to separate consumers from their money while providing little of value in return.
The fake Forbes story.
Misleading advertisements
Forbes was first notified of BrainStorm’s unapproved use of its trademark last November by an alert reader. The reader noted that the page in question, enhancebrainactivity dot com. seemed to use a Forbes article that did not ring true.
The story used an actual Forbes headline, “Viagra For The Brain,” from a 2002 Forbes Magazine cover story by Robert Langreth. However, the headline of the story had been altered to “BrainStorm Elite: Viagra for the Brain,” and the story crowed: “The previously banned genius pill is back and safer, stronger, and more likely [sic] to be banned again… then [sic]ever!” The URL of the article had been altered so that it looked as if it had been published in February 2014 – four years after Langreth left Forbes for another publication.
After I started looking into the ads, enhancebrainactivity dot com went down. But then the same information was used on three more web pages: strengthforyourbrain dot com, higherbrainIQ dot com, and forbesmemoryplus dot com.
The page also cited a Scientific American article by science writer Gary Stix, called Turbo-Charging the Brain. The advertisement claimed Stix called BrainStorm “the missing link in human evolution.” The phrase never occurred in the actual story.
Stix wrote via email that the actual point of his article was the opposite – that the notion that any substance performs as a “cognitive enhancer” is suspect. He was amazed by how many people saw the ads. “Someone who has a locker near mine at the Y came up to me and said he had seen something about me,” he writes. “I thought he might be referring to a story I had written. But it was actually that dumb ad.”
A "patient testimonial."
The Web page also included testimonials from patients supposedly enrolled in a clinical trial. “I woke up today (day 7) feeling like a new me,” one ‘participant’ wrote. “I had one of the most productive weeks I can remember and I feel like I owed it all to this tiny pill.” The advertisement also included an image of a brain scan lighting up 27 minutes after patients took a pill, and claimed that it improved grades for 87% of students.
I’ve never seen a clinical trial use these kinds of patient testimonials in 15 years of medical reporting. I checked: The University of Nottingham denies having anything to do with such a study of either BrainStorm Elite or any of the ingredients in the supplement. “The unit did not conduct this trial and knows nothing about it,” wrote Emma Thorne, a spokesperson for the university.
The "clinical trial."
Finger pointing
I contacted BrainStorm about these clearly misleading ads, and heard back from the company’s lawyer, Joseph D. Huser.
“The link you enclosed in your email was not published by BrainStorm Elite,” Huser wrote. “In the past my client has become aware of affiliate marketers who are misrepresenting its brand. To be clear, these misrepresentations are not being published by BrainStorm Elite and in such a case, a cease and desist letter is sent immediately.”
But BrainStorm Elite used the ads on its Twitter and Facebook pages. And, in any case, the Federal Trade Commission says that manufacturers are responsible for the actions of their marketing affiliates.
This altered image of a CNN documentary appeared on BrainStorm Elite's Facebook page.
Here is an image from the actual CNN show -- which does not mention BrainStorm Elite.
BrainStorm Elite’s Facebook and Twitter pages published, on January 17 and 18, what appeared to be a screen grab of a CNN special called “From Homeless to Harvard,” with the tagline: “Discover The Shocking Method That Doubled His IQ.” Except that the actual tagline when CNN ran that report was “What does an education mean?” Bridget Leininger, a CNN spokesperson, notes that the font used in the BrainStorm Elite version is not used by CNN.
The BrainStorm Elite Twitter page also posted the same brain image that was claimed to be from the NCTU study - the one that NCTU says never happened.
The fictional NCTU trial ends up on BrainStorm Elite's Twitter page.
And the strategy of Photoshopping real media stories seems a real concerted one. One of the pages briefly featured ABC’s Diane Sawyer. An online review of the product shows ads taken from “Discovery Magazine” – done in a typeface similar to that used by Discover Magazine, the science publication. It also claimed Leonardo DiCaprio uses the product.
“Is it generally considered a defense that you hired a marketer and the marketer made false claims? The answer is no,” says the FTC’s Cleland. “These are your agents, you have retained them, and you are responsible for what they do.” The FTC couldn’t comment directly on BrainStorm Elite, as it has not investigated the company, but Clelland says both marketers and their affiliates can be sued for any revenue they have brought in from misleading claims, and items purchased with the proceeds, such as boats or artwork, can be seized.
Finding the affiliates
After BrainStorm claimed the ads were the responsibility of its affiliate marketers, I decided to look for those marketers. A site called oDigger.com featured an offer to join a network called ValuLeads and use the Warren Buffett/BrainStorm Elite ad.. "We simply display offers pulled into oDigger form networks who have signed up with us," a representative of oDigger wrote via email. "We are in no way affiliated with that offer or any of its content, nor have ever run any traffic to it."
I found ValuLeads on the Web and called them. The man who picked up the phone told me, after I pressed him, that ValuLeads was not responsible for the ad, it just offered it to affiliate marketers as a middleman. He also claimed that the Warren Buffett/Forbes ad had never actually been live on ValuLeads’ network.
A WHOIS domain lookup of the BrainStorm Elite ad pages revealed that they were hosted by Amazon. The nameserver was through Domains By Proxy, which is part of Internet hosting site GoDaddy.com.
Amazon took down ForbesMemoryPlus when I complained, but would not reveal any information about who had posted the site. But GoDaddy was willing to share contact information of the registrant, after notifying them that it was doing so, on the grounds that the sites might violate Forbes’ trademarks.
For several of the Web sites, the registrant was Gregory Barbin, of Cardiff, Calif. When I called Barbin, he spoke to me briefly but gave me a phone number of a man who he said would “explain anything.” The person reached at that phone number said he knew nothing about BrainStorm Elite. When I got Barbin’s voice mail, it listed his business as carpet cleaning. I reached him again by telephone, and he said he had nothing else to add.
The BrainStormElite.com site itself was registered anonymously, and because it did not infringe on Forbes' copyright, we did not ask GoDaddy for information about the registrant. But BrainStormElite.org was registered to "HHF Life" with a phone number that belonged to a man named Troy Shanks, who styles himself as an "Internet Home Based Business Entrepreneur." His web site lists a Higher Health Foundation; a non-profit by that name was created in Indiana with Shanks as the registered agent, but it was dissolved in 2012.
"I have many irons in the fire when it comes to projects," Shanks writes on his website, "from health, to wealth, to blogging and establishing a community movement, my arms are ready and my eyes wide open to welcome as many of you as I can, to serve a higher purpose, help others create success, happiness and prosperity in life."
Shanks did not return several calls to the phone numbers listed on his website, or an email. Huser, the lawyer for BrainStormElite, did not respond to several follow-up emails and a phone call.
On March 28, while I was working on this story and after I contacted the company, a notification was added to BrainStormElite.com that the product was no longer for sale; however, there is no such notification on BrainStormElite.org, although the "order" button no longer exists. All of the Web sites using Forbes’ name disappeared, and BrainStorm’s social media accounts were scrubbed of the CNN photo. Whatever happens to BrainStorm, its strategy is alive and well: look at this advertisement that uses a look-alike of Men’s Health magazine to sell a testosterone supplement. Men's Health confirmed it had nothing to do with the ad and that its legal department knew about it; the ad was taken down within the past week.
A "Men's Health" ad much like the Forbes ones -- for another product.
Also on Forbes:
Gallery: 10 'Healthy' Habits That Drain Your Bank Account 10 images View gallery
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07234651edc2d911b6b1afbbae8e6991 | https://www.forbes.com/sites/matthewherper/2015/05/07/prescription-fish-oil-maker-hires-top-lawyer-to-sue-fda-on-first-amendment-grounds/ | Prescription Fish Oil Maker Hires Top Lawyer To Sue FDA On First Amendment Grounds | Prescription Fish Oil Maker Hires Top Lawyer To Sue FDA On First Amendment Grounds
Amarin Pharmaceuticals, which was rebuffed by the Food and Drug Administration in its effort to market its fish oil pill Vascepa to treat high triglycerides, is suing the agency, saying its First Amendment rights are being violated.
To make its case, the small drugmaker has hired one of the nation’s top free speech lawyers, Floyd Abrams of the New York law firm Cahill Gordon & Reindel, to make its case. Abrams and his colleagues are also representing several doctors who say they want to be able to get information about using Vascepa to lower triglycerides, because doing so may lower the risk of heart attacks and strokes. Right now, Vascepa is only approved for lowering extremely high triglyceride levels, above 500 milligrams per deciliter, while other drugs can be used about 200 mg/dL.
“It’s a First Amendment case,” says Abrams, who is also representing tobacco companies in a case that challenges the FDA’s ability to require graphic labeling. “It’s a case which challenges the ability and the power of the FDA to limit speech and potentially punish it notwithstanding that the speech is both important in nature and has every aim of serving the public. “
A great deal of the FDA’s marketing power comes from its ability to regulate speech. Drugs are approved for particular uses, and their manufacturers are allowed to market them to doctors and consumers only for the particular uses that have been vetted by the FDA. Doctors are allowed to prescribe medicines for anything they want, but if drug companies are caught encouraging those prescriptions, it is considered illegal. The bulk of the more than $13 billion in fines pharmaceutical firms have paid in recent years have been related to this so-called off-label marketing.
But Amarin’s lawyers insist that their case is drawn up specifically enough that it would not undermine the FDA’s power. Joel Kurtzberg, another lawyer at Cahill, says that a court could rule in Amarin’s favor but that other drug companies seeking to market outside their labels would still find themselves having to either go to court ahead of time or to make the marketing claims at the risk of regulatory action. “I don’t think it opens the can of worms that you talked about,” says Kurtzberg.
The legal filing, which is being made in the Southern District of New York, builds upon a previous case, U.S. v. Caronia, which involved Xyrem, a narcolepsy drug made by Jazz Pharmaceutical, and ruled "the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug."
The filing also makes several points in Amarin’s favor: that fish-oil-containing dietary supplements can make a claim that “supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease;” also that other drugs to lower triglycerides, like niacin and TriCor, both sold by AbbVie , and the fish oil pill Lovaza, made by GlaxoSmithKline , are allowed to be marketed to a broader swath of people with high triglycerides.
But the claim softpedals the scientific debate of whether any of the medicines do any good. Recent randomized controlled trials of fish oil, including one published in the Journal of the American Medical Association and another in the New England Journal of Medicine, have shown little benefit from taking it to prevent heart attacks. Vascepa is higher dose and more pure, and a similar fish oil product seemed to show a benefit in a clinical trial in Japan, but the data remain murky, many cardiologists say.
“We have no idea whether these triglyceride drugs work and that needs to inform all of our decisions about whether they’re available, how they’re promoted, and who should use them,” says Harlan Krumholz, the Harold H. Hines, Jr. Professor of Medicine at Yale University.
Sales of Vascepa were just $54 million last year. Amarin is conducting a big study of whether Vascepa prevents heart attacks and strokes, but it will not be completed until 2017.
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e4da9e35100ce27462dc8fe15367b1a3 | https://www.forbes.com/sites/matthewherper/2015/05/14/former-genentech-researchers-raise-217-million-for-company-to-fight-alzheimers-and-parkinsons/ | Genentech Brain Trust Leaves With $217 Million For New Startup To Fight Alzheimer's And Parkinson's | Genentech Brain Trust Leaves With $217 Million For New Startup To Fight Alzheimer's And Parkinson's
Marc Tessier-Lavigne
Three former top researchers at Genentech , the legendary biotech that is now part of Roche Holding , have raised $217 million in venture capital to start a new company, Denali Therapeutics, focused on treating and curing neurodegenerative diseases like Alzheimer’s, ALS, and Parkinson’s.
The news is another sign of both the large amounts of money available to all biotechnology startups and for a financial turnaround for research efforts against brain diseases that have been tough to beat. NeuroPerspective, a newsletter that tracks neurological treatments, says in the past five years the number of drugs being developed by large drugmakers for brain and nervous system disorders fell 50% to 129 – but that last year, investors poured $3.3 billion into the field, more than in any of the last ten years. The raise for Denali is a series A, the very first round of getting funding for a new company. It is the largest such round in biotech history.
One reason for the overstuffed purse: One co-founder, Denali’s chairman of the board of directors, is Marc Tessier-Lavigne, a well-known neuroscientist and president of Rockefeller University in New York. He served as Genentech’s head of drug research during its legendary run in the late 2000s, before the company was bought by Roche in 2009. He’s also giving up a board seat at pharma giant Pfizer in order to make time for his new company.
“The science in the field has been breaking open and this has been accelerating over the past decade,” says Tessier-Lavigne. “Denali is based on the idea that the time is right to tackle these diseases systematically and deeply.”
Denali CEO Ryan Watts
Leading day-to-day operations as chief executive will be Ryan Watts, until now director of neuroscience at Roche’s Genentech division. Alex Schuth, who headed technology innovation and diagnostics business development at Genentech, is the third co-founder. The company will be based in San Francisco.
The company is named after the tallest mountain in North America. “For me it means an inspiring challenge,” says Watts. “We wanted a name that was recognizable that represents a huge unmet need.”
To climb this particular mountain, Watts says that Denali will be avoiding already crowded areas in the development of drugs for diseases like Alzheimer’s. For instance, companies including Biogen, Eli Lilly , Merck, and Genentech are all trying to slow the progression of Alzheimer’s with drugs that block a substance called beta amyloid, which is present in tangles in the brains of Alzheimer’s patients. Watts says Denali won’t pile in.
Instead, Watts sees a new generation of drug targets emerging from human genetics. He says that just as oncogenes – cancer genes – have lead to a flood of cancer drugs, newly discovered genes linked to degenerative brain disease (the Denali guys called them degenogenes) will provide a basis for a new generation of brain medicines.
Denali co-founder Alex Schuth
Denali will also focus on how inflammation drives brain disease; how the trafficking of substances between cells is involved in Parkinson’s and Alzheimer’s; and on factors that influence how brain cells die that are common to all brain diseases. Already, the company is looking at least 12 different drug targets in these areas, though it will not disclose more about them yet.
Investors include Fidelity Biosciences, ARCH Venture Partners, Flagship Ventures and the Alaska Permanent Fund (represented by Crestline Investors). Additional investors include sovereign wealth funds, public mutual funds and private family offices, with significant reserves for additional future financing.
Robert Nelsen, co-founder of ARCH Ventures and an investor in other hot biotech startups like JUNO Therapeutics and Agios, both of which now sport $4 billion market capitalizations, says that combining forces in a big effort is already drawing attention among researchers even before the company officially launches.
“The best scientists in the world are now calling us, “ Nelsen says. The next step, he says, is engaging the Food and Drug Administration about how to develop brain drugs more quickly, as has happened in HIV, hepatitis C, and cancer. “ You can’t wait 10 or 20 years for the perfect study in Alzheimer’s when it’s going to cost us a trillion dollars in today’s dollars by 2050. The societal cost of these diseases is mind-blowing.”
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41d292eaa897982cb4ece18625c723bc | https://www.forbes.com/sites/matthewherper/2015/06/09/promising-result-in-postpartum-depression-creates-hope-for-inventing-new-psychiatric-drugs/ | Severe Depression Vanished In Four New Mothers After They Took This Drug. Is It For Real? | Severe Depression Vanished In Four New Mothers After They Took This Drug. Is It For Real?
In the months after their children were born, all four women plunged into severe, debilitating sadness. Antidepressant treatments didn’t work. They were admitted to the hospital. The women’s average score on a questionnaire called the Hamilton Rating Scale for Depression was 26.5; severe depression starts at 24. Normally, experts say, their illness might have lasted years.
Then each of the four was given an injection of an experimental epilepsy drug, SAGE-547, made by a tiny Cambridge, Mass., biotechnology firm called Sage Therapeutics. Within 60 hours, their scores on the Hamilton Scale sank past seven – the boundary for having any depression at all – to an average score of 1.8. Their symptoms had basically disappeared.
“We feel this is a very strong signal, because it is a robust response,” says Samantha Meltzer-Brody, director of the perinatal psychiatry program at the University of North Carolina Center for Women's Mood Disorders and lead investigator of the study. “It looks very exciting,” adds Dr. Adele Viguera, a psychiatrist at the Cleveland Clinic who was not associated with the study. “It’s only four patients but what’s exciting is that you can treat someone relatively quickly for post-partum depression.”
In early morning pre-market trading, shares in Sage Therapeutics increased 20% to $90.
But two former presidents of the American Psychiatric Association warn that the results are still too early to trust. “It’s as preliminary as preliminary can be with human subjects,” says Nada Stotland, a professor at Rush Medical College in Chicago.
Adds Columbia-Presbyterian psychiatry chair Jeffrey Lieberman: “The problem is it’s such a small number of people. It’s an interesting target and a plausible mechanism of action. At this point it’s a theory with some anecdotal supporting evidence and you can’t really say much more.”
Sage Therapeutics CEO Jeff Jonas
Sage Therapeutics, however, does have more to say. The data are positive enough that the company is advancing SAGE-547 into a larger placebo controlled trial to see if the dramatic benefits hold up. It will also start testing another experimental drug, one of more than 700 related compounds the company has synthesized, as a depression treatment. The hope is that it can find a pill that could act as a new treatment for post-partum depression, which affects one mother in five, and other mental illnesses. This could be a staging drug for creating medicines for mental illness, an area Big Pharma has been abandoning.
For Sage’s chief executive, Jeffrey Jonas, this is part of a larger project: figuring out how to develop psychiatric drugs in a new, less failure-prone way. Jonas is a psychiatrist – he trained at Harvard – who worked on psychiatric medicines at Upjohn, Forest Laboratories , and Shire . He’s watched as a drug company exodus from the field, as big names like GlaxoSmithKline , Bristol-Myers Squibb , and AstraZeneca, fled and, according to the newsletter NeuroPerspective, the number of central nervous system drugs developed by big firms fell 50%.
Sage’s first drug, SAGE-547, has until now been aimed at epilepsy, and not just regular epilepsy, but a severe form called refractory status epilepticus. These are seizures that don’t end. Patients are generally put in a medical coma in the hopes that, if their brains are allowed to rest, the seizures will stop. Sometimes it works, sometimes it doesn’t. Take the below video, produced by Massachusetts General Hospital, of a man named Raj whose seizures kept him in a coma for five months. Doctors there gave him the drug, and after several days, he opened his eyes. He could follow commands.
SAGE-547 is a hormone released by nerve cells that triggers receptors of the GABA system, the main inhibitory system in the brain. Jonas believes that drugs like it could have an effect well beyond epilepsy.
Many drug companies, Jonas alleges, have become obsessed with thinking of the brain as if it were a tumor, which could be stopped if only you could understand the genetic mutations that cause its problems. In cancer, genetic mutations lead to the overgrowth of cells, and that is the disease. But the brain is different. A gene might leave a patient vulnerable to depression, but fixing that gene might not fix the depression, he argues. And it might not matter what caused the depression, either. Like a cough, it might always be treated the same way.
“It’s like saying if I break my arm in a ski accident or in a car door, the treatment is not going to be any different,” Jonas says. Figuring out a genetic cause is not the answer, he argues.
Instead, Jonas takes another lesson from cancer drug development. One reason that cancer drugs have moved ahead so quickly is that researchers have found serious diseases in which they can quickly get dramatic, early results. That’s what Jonas has done in severe epilepsy. Now we know SAGE-547 can have a dramatic effect on the brain. Now he’s testing the same molecule in post-partum depression, and he ticks off a broad swath of other illnesses it might affect: “Anxiety, suicidality, depressive mood,” Jonas says. “So we are now faced with a wealth of opportunity.”
First he has to prove that the early hint seen in these depressed mothers is real. No clinical trial had ever before tried using an injection to treat post-partum depression. Could having gotten the shot have led to a dramatic placebo effect? Stranger things have happened. Jonas doubts it, but admits that he needs a placebo-controlled trial to know for sure.
And if it works, he doesn’t even think Sage-547 will itself become a depression drug. Instead, he hopes to use information about blood levels of the drug to help pick another molecule from SAGE’s chemical libraries – to, in his words, “hone in on what we hope will be an ideal oral agent for this disorder.” Ideally, it would be a pill, with few side effects. It could take years to get there.
There’s a lot of work to be done. But at least Jonas has a drug – and a plan.
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5e82a1069239a389917e0d3f1b4d7a3e | https://www.forbes.com/sites/matthewherper/2015/08/10/bill-gates-and-13-other-investors-pour-120-million-into-revolutionary-gene-editing-startup/ | Bill Gates And 13 Other Investors Pour $120 Million Into Revolutionary Gene-Editing Startup | Bill Gates And 13 Other Investors Pour $120 Million Into Revolutionary Gene-Editing Startup
Four years ago, the protein called CRISPR-Cas9, an enzyme that bacteria use to attack viruses that infect them, was unknown to humans. Now it is ubiquitous in science labs as the most efficient way of cutting-and-pasting DNA yet invented. Wired Magazine, in a breathless cover story, just called it “The Genesis Engine,” instructing readers to “buckle up” because the easy DNA editing CRISPR enables will change the world. And now at least one CRISPR-focused company has the cash to back up the hype.
Editas Medicine, based in Cambridge, Mass., already had money. Founded in November 2013 with $43 million from Third Rock Ventures, Polaris Ventures and Flagship Ventures, it was the first big CRISPR effort out of the gate. The company says that money has not been spent. In May, Juno Therapeutics, which is developing cell therapies for cancer, inked a collaboration that gave Editas $25 million upfront and another $22 million in research support. Any products that result could deliver Editas another $250 million.
But those investments are dwarfed by today’s announcement, which will put $120 million into the tiny company’s bank account – enough, Editas says, to keep it running for a projected three years. The lead investor is a newly created firm called bng0, a select group of family offices led by Boris Nikolic, who was previously a science advisor to Bill Gates. Both Editas and Gates’ office confirm that the Microsoft billionaire, who is the world’s richest man, is among the bng0 backers.
Bill Gates: Beyond Microsoft, Money, Malaria. An eBook From Forbes From PCs to vaccines, find out how Bill Gates made his mark on the world.
Also included in the $120 million funding round (take a deep breath): Deerfield Management, Viking Global Investors, Fidelity Management & Research Company, funds and accounts managed by T. Rowe Price Associates, Inc., Google Ventures, Jennison Associates on behalf of certain clients, Khosla Ventures, EcoR1 Capital, Casdin Capital, Omega Funds, Cowen Private Investments and Alexandria Venture Investments.
“They all appreciate the vast potential of this science,” says Katrine Bosley, the chief executive of Editas. “The heart of the conversation we had with everybody is how you translate this very exciting but young science into treatments, into therapies.”
It’s a big leap for a technology that has yet to even be tried in patients – especially since the intellectual property landscape around CRISPR-Cas9 is treacherous. Jennifer Doudna and Emmanuel Charpentier published the first paper detailing how to use the enzyme to cut DNA. They filed for a patent for using it to edit the DNA of cells with nuclei – like those of plants, animals, and people – too. But Feng Zhang of the Broad Institute filed a separate patent on using it in cells with nuclei, and it was granted first.
Doudna, originally an Editas founder, has licensed her patent to another Cambridge, Mass.-based company, called Intellia. Charpentier has licensed to CRISPR Therapeutics, based in Basel. Zhang’s patent is licensed to Editas.
Jim Flynn, a managing partner at Deerfield Capital Management, says he thinks Editas has a very strong intellectual property position, but that it wasn’t his most important concern. Better to get to market first, he argues, than to have the best IP.
“Your worst case scenario if you’re first to the market with something that is going to create a survival benefit in a population is maybe you have to pay a royalty, maybe there is a cross license,” Flynn says.
Echoes Hans Bishop, the chief executive of Editas’ cancer partner, Juno: “As a company, from a capability side, Editas is the leader.”
Editas CEO Bosley says creating new treatments is her new focus. Other companies are probably already using CRISPR-Cas9 to try and discover new drugs. But Editas is focused on gene therapy, on using viruses or other methods to deliver the CRISPR-Cas9 protein into the cells of sick patients and edit the very DNA that is making them ill.
The first project likely to be tried out in patients, she says, is a treatment for Leber's congenital amaurosis type 10, a genetic form of blindness. The disease is a good choice for a first attempt at making CRISPR-Cas9 work, she says, because it is in the eye, where gene therapies are easier to deliver, and because it is caused by a single genetic misspelling that can be deleted out. It will be much harder to rewrite genes than to make simple deletions.
Even so, Bosley said, it turned out to be harder to fix LCA-genes in cell culture than Editas scientists expected. The CRISPR simply didn’t cut in the right place, and they had to figure out how to cut the DNA in two places in order to fix the broken gene. She says her team is also working hard on the Juno project. And Editas is working on hemoglobinopathy, a type of genetic condition in which the molecule that carries oxygen in red blood cells is defective. That will be a tougher project: it will involve not just cutting out a DNA misspelling, but actually editing a gene.
All of this could take years, and it could be a long time before there is an initial public offering or sale that would offer the investors a payoff on their investment. Flynn, the Deerfield partner, says he’s happy to wait. His fund, he says, has a 12-year time horizon. “We’re very comfortable we can weather any storm that is likely to come.”
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d2dfb4aeef5f7603e06b407599929249 | https://www.forbes.com/sites/matthewherper/2015/08/17/patient-death-does-not-augur-doom-but-kite-pharma-needs-to-shut-its-big-mouth/ | Patient Death Does Not Augur Doom, But Kite Pharma Needs To Shut Its Big Mouth | Patient Death Does Not Augur Doom, But Kite Pharma Needs To Shut Its Big Mouth
This morning Kite Pharma confirmed that a patient had died in a trial of its cell therapy for a form of blood cancer. Market rumors about the death had pushed the company’s stock down 16% on Friday.
The stock has recovered most of its losses, and rightly so, because the news of a single death in a study of cancer patients who had been failed by everything medicine had to offer is actually, well, not news. And Kite offered new details on the trial that mean that it is proceeding quickly on the clinical trial that could allow its treatment to reach the market by 2017. Maybe the stock should be up.
But on a conference call this morning, Kite chief executive Arie Belldegrun decided to try to put out the fire by disclosing far more about the patients in Kite’s clinical trial than could possibly have been necessary, displaying a recklessness that should concern investors moving forward as Kite races with rivals like Juno Therapeutics and Novartis to develop a series of therapies that really could someday change the way that cancer is treated. There’s only good news about Kite’s treatment and its prospects, but Arie needs to learn to shut his big mouth.
Late last week, as Kite was announcing that it was initiating a patent challenge to one of the patents licensed by Juno, its competitor, rumors about a patient death started to circulate. Sick cancer patients die, and the news of a single death shouldn’t mean anything. But investors are tense about the valuations of companies developing this new type of therapy, called CAR-T, for chimeric antigen receptor t-cells, which has made cancer melt away by harnessing the immune system. A few times, in early studies, CAR-T has stimulated the immune system so much that it kills the patient.
Tony Butler, an analyst at Guggenheim Partners, put out a note saying that he had spoken to Kite management and understood that there was a death. Butler wrote that the death did not seem to be related to the immune response caused by CAR-T, but that he was unable to confirm that with Kite. He said that his understanding was that the study was not paused to ensure patient safety.*
Normally, a company would not release any details from a clinical trial until it was done. But having told one analyst about details from the study, Kite had a duty to inform all of its investors. This morning, Kite held a conference call and issued a press release confirming the death and offering more details.
"There is a very good reason for not publicizing information in a clinical trial,” Belldegrun said on the call. First, there is a need to protect the patients in the study. But there is also always a risk that releasing information early can bias the final results, which is why clinical trials are kept under wraps until it is time to present them.
But Belldegrun said KITE negotiated with the American Society of Hematology, the society at whose meeting the results are going to be presented, to provide more detail. Some of what he said should ease investors’ worries and poses no risks to the final results of the study.
Most importantly, KITE has discussed the result with the Food and Drug Administration, and Kite says the FDA never told it to stop the study. That distinguishes this from the deaths that occurred in a trial of one of Juno’s CAR-T therapies, which were the results of patients’ hyped-up immune systems and did force a trial to stop. It’s worth noting that those concerns passed, too. The Juno studies re-started, and Juno went on to have a successful initial public offering and now sports a $3.6 billion market capitalization, $1 billion more than Kite. Really: this death probably never meant anything for Kite’s future.
More positive stuff: Kite has successfully been enrolling patients in a multi-center clinical trial with a central manufacturing site, meaning it's overcoming some of the big hurdles with CAR-T therapy. Belldegrun re-iterated that if all goes well, Kite’s treatment for diffuse large B-cell lymphoma could be on the market in 2017. All good news.
But also Belldegrun provided more detail about the clinical trial. He said that already patients had had complete responses, meaning their cancer vanished, at least temporarily, and that tumors were “melting away.” That’s basically revealing details of the efficacy results of the study. If we’re worried about biasing the study results, that’s exactly what he should not have said.
All of this may not matter. It’s very possible, in the white-hot environment for biotechnology stocks, that the valuations of companies like Juno and Kite are ahead of themselves, so no wonder investors are skittish. But at least in their initial uses – treating very sick patients – these treatments are showing dramatic success. The question is whether the market is now assuming that CAR-T will work not only in these initial cancers, but others, too.
The need to balance the needs of public investors with those of science is as old as the biotechnology industry – it is why science by press release is a thirty-year-old institution now. And none of this noise will signify much if Kite’s trial is successful. If there’s any takeway for investors, it’s that Kite shouldn’t have confirmed the death, nor should it have released even more information about how well patients in the trial were doing. And that should maybe make them a little nervous about Kite’s management.
*A previous version of this story said that Butler confirmed that the death had occurred. He said that he understood that the death occurred in speaking to Kite, but did not confirm it.
Here is the full text from his note:
"In speaking to Kite, we understand three things: 1) A death in a patient with DLBCL did occur. We assume it was disease-related similar to deaths that have occurred in clinical studies at the National Cancer Institute (NCI); 2) We do not believe it was related to cytokine release syndrome (CRS), but we are unable to confirm this point and, moreover, we do understand there will be no clinical hold as a result of the occurrence; 3) Abstracts to the American Society for Hematology (ASH) in December have been submitted by Kite and its investigators. We understand the Phase II portion of this registration trial (safety observations in the lead-in Phase I portion of the trial leading to a Phase II) will begin before abstracts become available to the public (most likely November). We assume that the Phase II portion of the study would not be allowed were there expectations of a clinical hold. We would be buyers of KITE stock on this weakness."
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ca49c2285cad3e210cb4b48230045b52 | https://www.forbes.com/sites/matthewherper/2015/10/12/eli-lillys-good-cholesterol-drug-goes-bad/?utm_source=followingimmediate&utm_medium=email&utm_campaign=20151012 | Eli Lilly's Good Cholesterol Drug Went Bad. Here's What That Means For Pharma | Eli Lilly's Good Cholesterol Drug Went Bad. Here's What That Means For Pharma
Albert Einstein never said that the definition of insanity is doing the same thing over and over again and expecting a different result. But whoever did say it was probably talking about a pharmaceutical executive.
This morning, Eli Lilly announced that evacetrapib, its experimental drug to raise good cholesterol, failed to prevent patients from getting heart attacks and strokes in a large clinical trial. It is the third similar medicine to fail in expensive studies by three different drugmakers, dashing hopes for a new kind of treatment that might have helped millions of patients and calling into question the risky tendency of pharmaceutical executives to spend hundreds of millions of dollars on studies that have a low probability of succeeding.
In its release, Lilly wrote that that the largest study of evacetrapib, was being stopped because of “insufficient efficacy.” Steven Nissen, the Cleveland Clinic cardiologist who ran the study, says that the results can’t be explained because the study was too small or because too few heart attacks and strokes occurred. “The drug didn’t work,” Nissen says.
That harsh reality will be felt across the pharmaceutical industry. It creates big doubts over whether another similar drug, from Merck , will amount to anything. It bolsters the prospects of two new, high-powered cholesterol-lowering shots: Repatha, made by Amgen , and Praluent, from Regeneron and Sanofi , who now won’t have competing pills. For Esperion Therapeutics, a tiny start-up, the results are mixed: The potential market for its medicine just got bigger, but it may now take longer to get the drug approved.
Evacetrapib is a drug designed to boost levels of “good cholesterol” in HDL particles by blocking the cholesterol ester transfer protein, or CETP. For years, doctors largely believed that any HDL-boosting drug would prevent heart attacks and strokes. People with low HDL, after all, seemed to be at higher risk.
But the genetic data on people who had high levels of HDL because of changes in their CETP genes were mixed. People in Japan who had no CETP function – and super-high HDL levels – didn’t seem to have fewer heart attacks. Caucasian people with slight defects in CETP, and slight boosts in HDL, seemed to have a 4% reduction in their risk of heart attacks and strokes – significant, but not very big.
Three times, CETP-blocking drugs failed to help patients. Pfizer bet its future on a giant study of a CETP inhibitor, planning to create a combo pill to extend the life of Lipitor, the best-selling drug of all time. The drug actually increased the death rate in a large study. Roche tested a second CETP inhibitor, invented by Japan Tobacco, and found no benefit. Lilly’s failure makes success for Merck seem unlikely.
“We now have three different CETP inhibitors that have all failed,” says Sekar Kathiresan, a Harvard geneticist. “The odds of the fourth one succeeding are low.”
In fact, Kathiresan’s work seems to show that the whole idea that boosting HDL prevents heart attacks may just be wrong. In a 2012 study published in the Lancet, he showed people with genetic mutations that boosted HDL didn’t have fewer heart attacks and strokes. Clinical trials of other HDL-raising drugs have failed, too.
The hope for CETP inhibitors was that they also lowered LDL cholesterol. Investors were becoming more optimistic, according to polls conducted by ISI Evercore analyst Mark Schoenebaum. Amgen even bought the rights to a CETP inhibitor for $300 million last month. Oh, well.
The new cholesterol-lowering shots, Praluent and Repatha, represent an alternative approach to developing drugs. These drugs target a protein called PCSK9, and people whose genes don’t make it have much lower levels of heart disease. That strategy – creating drugs where genetics are clear – may represent a way to prevent expensive failures.
But such genetic data doesn’t exist for every new medicine. For instance, it doesn’t exist for the drug being developed by tiny Esperion, code-named ETC-1002. The stock has been hammered because Esperion told investors that the Food and Drug Administration might ask it to do a big study like the one evacetrapib failed in to prove ETC-1002 prevents heart attacks and strokes. Previously, Esperion claimed that the study wouldn’t need to finish until after the drug hit the market.
There are other factors that matter. In contrast to drugs that raise HDL, medicines that lower LDL cholesterol and do nothing else all seem to have prevented heart attacks and strokes. Even a weak drug, Merck’s Zetia, recently showed such a benefit in a large clinical trial. Esperion shares, by this logic, look cheap: an effective cholesterol-lowering drug with an enterprise value of just $350 million.
The bigger question is whether investors should take the CETP story as a cautionary tale about other big, risky drug development programs. For instance, Lilly’s other big pipeline asset, solanezumab for Alzheimer’s disease, has scary parallels to today’s failure. The genetics here are better. But a similar medicine from Pfizer failed, and solanezumab itself failed in a previous study. Sure, things might be different next time. But do we really want to bet on that?
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3410d0a6d8d17542937d4cb8860c45ca | https://www.forbes.com/sites/matthewherper/2015/10/21/23andmes-triumph-and-the-long-road-ahead/ | 23andMe's Triumph -- And The Long Road Ahead | 23andMe's Triumph -- And The Long Road Ahead
This morning 23andMe announced that it’s back, once again offering direct-to-consumer genetic tests from which consumers will draw health conclusions. This time it has the approval of the Food and Drug Administration.
It was a long road – appropriately, the FDA told 23andMe to stop giving consumers health data 23 months ago – and the 23andMe that is returning looks very different from the one that went into sleeper mode back then.
Instead of offering real-time information on what genetic research had to say about any disease risk a patient might have, now 23andMe is focusing on giving consumers “carrier status” information on 35 genes that can cause diseases. This is mainly of interest to prospective parents. Do you have a gene that can cause sickle cell anemia? Does your spouse? If both of you come up positive, your child has a 25% chance of having the disease.
The new 23andMe test will also cost $199, double the previous price. “I think at $199 we’re an exceptional value,” says Anne Wojcicki. But Wojcicki also sees the decision as the beginning of a future where 23andMe will work with the FDA to make more genetic testing available. She’d like to get back to giving people information about what they can learn from their genes about which medicines they should or shouldn’t take, or what conditions they are at risk for. “At some point that is the mission of the company and that is what we aspire to get back to.”
In the meantime, there are more pressing executional matters. Wojcicki says the company has not settled on an FDA-compliant marketing plan, but would love to do so this holiday season.
The story of 23andMe’s return should serve as both encouragement and a warning to companies (think Theranos) that hope to disrupt the healthcare system. You can get a lot of you want, but it will take longer than you expected and will take a lot more work. The first thing that Wojcicki had to do was admit she was wrong.
During a period when her staff had been undergoing upheaval and she was in the midst of a separation with ex-husband Sergey Brin, Wojcicki had been shocked to find out that the FDA had thought 23andMe was stonewalling. “It never, ever occurred to me that we would just have to stop returning the health reports,” she says.
Wojcicki and 23andMe president Andy Page went on a listening tour to figure out what they didn’t know. (Inarguably, they should have figured that out before.) One of the people they met, through a common investor, was Kathy Hibbs, the general counsel at Genomic Health. During a meeting when they were talking to her about what they needed to learn, they leaned in and offered her the job.
Hibbs said no – she had a job – but kept thinking about the offer. The question of whether and how genetic test results could be given to consumers was one every other company in the space had dodged by involving physicians. 23andMe now had an FDA warning, and that would mean working out an answer. To a regulatory lawyer, it was a huge opportunity to set precedents that would shape the future of health care.
It made Hibbs’ parents nervous, but the new job didn’t mean moving her family. So she took it. Wojcicki gave her five binders detailing every interaction that 23andMe had with the FDA, and Hibbs proceeded to read them in their entirety seven times.
What Hibbs found was that 23andMe and the FDA were not even speaking the same language. The FDA is guided by laws and regulations that limit what it can say, and 23andMe wasn’t picking up on the agency’s cues. FDA officials would leave 23andMe an opening to change the way carrier testing was regulated, for instance, and 23andMe would ask an unrelated question.
The big issue for the FDA was that the agency needed proof that 23andMe could convey to consumers what a test result meant. The agency insisted that 23andMe do studies to prove comprehension, and that those studies include not just the educated and relatively wealthy types who have been 23andMe’s customers so far but an entire cross-section of the U.S. population. The initial studies were done in Bloom Syndrome, where 23andMe got its first FDA approval. But the FDA wanted to see a second set of data, in cystic fibrosis, which is more complicated because there are different genetic mutations that carry different risks. “The FDA cares about every word on the page here,” says Brad Kittredge, 23andMe’s vice president of product.
In the end, the agency was fine with 23andMe’s marketing so far. The two big questions are how fast 23andMe will be able to expand what it can offer consumers, and how interested consumers will be in the limited offerings the company currently has for sale. When the FDA stopped 23andMe two years ago, the company was on a publicly declared mission to get to 1 million costumers. It has managed to pass that figure. More than that, it can monetize that data by doing more than selling tests. 23andMe always planned to sell access to its data to drug companies that could use it for drug research, and it is now also searching for new medicines in house.
“If you are somebody who has a disease you are not complaining when someone starts to do work for you,” Wojcicki says. “That is your hope.”
There could be more controversies ahead. As part of its new design, 23andMe will tell users if law enforcement agencies ask for their genetic information. So far, the company has never been forced to give that data up. But the idea is likely to make those who are uncomfortable with its business model more uncomfortable.
At the very least, Wojcicki has been able to convince her investors. As reported in the most recent issue of Forbes, 23andMe raised $115 million from investors including Fidelity Management & Research Company. The investment values 23andMe at $1.1 billion.
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82052f3de749a064c3b1ae5a2fdaaeeb | https://www.forbes.com/sites/matthewherper/2016/02/04/here-are-some-solutions-to-the-martin-shkreli-problem/ | After The Martin Shkreli Circus, How Can We Fix Drug Pricing? | After The Martin Shkreli Circus, How Can We Fix Drug Pricing?
Martin Shkreli listens during a hearing of the House Oversight and Government Reform Committee on... [+] Capitol Hill February 4, 2016 in Washington, DC. (BRENDAN SMIALOWSKI/AFP/Getty Images)
There was no doubt that hauling Martin Shkreli, the infamous young pharmaceutical entrepreneur, in front of Congress would be dramatic. Of course it was. But did it get us any closer to preventing the next Martin Shkreli from taking an old drug and raising the price 5,000%?
At the hearing held this morning by the U.S. House of Representatives Oversight Committee, Elijah Cummings (D-MD) assumed the manner of a preacher, begging Shkreli to turn his life around. “You can go down in history as the poster boy for greedy drug company executives or you can change the system,” Cummings said.
Shkreli smirked. The committee wanted to know how his company decided to raise the price of a drug called Daraprim, for a disease called toxoplasmosis, by 5,000% to $750 per pill. Shkreli had no answers. He repeatedly took the fifth--answering only one question, on the pronunciation of his name--and, just after he left, he sent a tweet.
Hard to accept that these imbeciles represent the people in our government. — Martin Shkreli (@MartinShkreli) February 4, 2016
The hearing revisited in miniature what went wrong for Shkreli in the first place. He couldn’t not smirk, he couldn’t not tweet. "A jury would love to convict somebody if he acts that way while he’s on trial,” said Representative Jimmy Duncan (D-TN).
Howard Schiller, the chief executive of Valeant Pharmaceuticals , should have been at least as good a target as Shkreli. The committee had turned up an email from Schiller himself, back when he was Chief Financial Officer, saying that 80% of Valeant’s sales growth came from increasing prices. Yet Schiller kept calmly repeating that Valeant had learned from his mistakes.
In contrast, Nancy Retzlaff, the chief commercial officer of Turing Pharmaceuticals, was left to take abuse for her former boss’s tweet and to keep insisting that the company had been thinking about patients when it decided to raise the price 5,000% to $750, that she was OK with it only because the company was committed with making sure every patient could get the drug, that the company would cover their expensive insurance copays, and that 60% of the money it made would be put into research and development for a new toxoplasmosis drug.
Congress, for its part, showed itself to be full of ignorance about how the medical system and pharmaceuticals work. Blake Farenthold (R-TX) didn’t seem to understand that the Food and Drug Administration can’t approve generic drugs without data proving they work the same way in the body as the branded versions. Congressmen stumbled over the complicated relationships between insurers, drug companies and hospitals. They kept focusing, though, on why nobody was making a generic to take away Shkreli’s market share given that Daraprim is a 60-year-old drug.
“The bottom line is we’ve got a broken market,” said Representative Peter Welch (D-VT) “I think anything we can do to help with the FDA we should do that. You’ve got market power without competiton and it is resulting in ripoffs most glaringly represented by Mr. Shkreli.”
The problem here is that the U.S. health insurance system, including big companies like UnitedHealthcare, Anthem and Express Scripts , cannot do a good enough job controlling healthcare costs. That’s why Shkreli was able to charge $750 per pill for a drug that, in government programs like Medicaid, he sold for only a penny.
Congress seems as if it could use some help figuring out how to fix that broken market. Keep in mind that some drugs, particularly new ones, need to be expensive. Congress’ whining about the cost of new hepatitis C drugs is, for instance, highly misguided. But that doesn’t mean that we can’t make sure that the market is fair.
Here are six solutions I offered in my recent Forbes Magazine piece, "Solving Pharma’s Shkreli Problem." I’m presenting them here verbatim to save you a click.
Make the system transparent.
Right now we don’t know the real price of drugs, because all the bargaining happens on the rebate side. Markets work better when everyone can see prices. This would hurt pharma’s profits and negotiating power but help its image. Give the FDA the ability to treat a price increase of an off-patent drug as a shortage. This would have stopped Martin Shkreli’s price hike on Daraprim in its tracks. The drug sells for $20 in the U.K., where Glaxo sells it. In cases of a declared drug shortage, the FDA can allow foreign drugs to be imported. Right now the FDA is not allowed to consider price in deciding whether there is a shortage (or any other situation). It should be allowed to. A related thought: When a dramatic price increase happens, allow the FDA to fast-track any generic that comes along. Pay different amounts for cancer drugs depending on the type of cancer. We pay the same price for a dose of a cancer drug whether it is likely to add years to a patient’s life or just weeks. That doesn’t make sense. Peter Bach at Memorial Sloan Kettering has proposed changing that so you pay different amounts for Avastin in treating colon cancer versus lung cancer, for instance. Express Scripts ngIf: ticker ESRX +0.00% ngIf: show_card end ngIf: ticker says it is going to try it out. “This is a necessary step if we’re going to start paying for drugs based on how well they work,” says Bach. Bring down the hammer for rare-disease drugs. One idea floating around Washington: Many new medicines are for rare, or “orphan,” diseases. (They’re called that because drug companies used to ignore them; not anymore.) Under the 1983 Orphan Drug Act, designed to spur pharma investment in rare disorders, companies are given tax benefits and longer protection from generics if they develop an orphan drug. With big pharma hyper-focused on treating rare diseases anyway, the law should be modified so price increases above a certain level take those protections away. Allow Medicare to negotiate drug prices. In other words, use the U.S. government’s buying power to force prices down. The worry here is this could turn into de facto price controls. Give drug companies skin in the cost-savings game. Novartis ngIf: ticker is launching a new heart failure drug, Entresto, that reduces the risk of patients landing in the hospital by 21%, according to a large trial published in the New England Journal of Medicine. Novartis Chief Executive Joseph Jimenez says he has worked out a deal with insurers where Novartis will get paid extra if patients stay out of the hospital. “It is possible to give some of that value back to the system and to generate enough value for Novartis that my shareholders will say, ‘That’s a good place to invest,’ ” Jimenez says.
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2f07115fbf3a1a9478023d06df60e891 | https://www.forbes.com/sites/matthewherper/2016/03/23/biotech-roars-back-on-forbes-list-of-the-top-venture-capitalists/ | Biotech Roars Back On Forbes' List Of The Top Venture Capitalists | Biotech Roars Back On Forbes' List Of The Top Venture Capitalists
Gallery: Top Biotech Investors On The 2016 Midas List 7 images View gallery
For years, venture capitalists who bet the seed money used to start small biotechnology companies have played second fiddle to their colleagues in the tech world, where a bet of a few million dollars on some college dude in a hoodie can rapidly turn into the next Facebook or AirBnB. In biotech–which almost always means drug discovery–the timelines are longer, the costs higher. And that, sadly, often means that the financial returns are lower.
But this year, biotechnology made a big statement on Forbes’ Midas List, which has tracked the performance of big-name VCs for 16 years by ranking them based on how big their stakes were when their companies were sold or went public. Last year, there were only five biotech venture capitalists on the Midas List; this year there are seven. What’s more, they ranked higher than ever before.
What drove the outperformance? A boom in both the biotech stock market and in biotechnology mergers and acquisitions. Between March 2011 and July 2015, the iShares Biotechnology Index increased 293%. Each year there were more initial public offerings raising more money that the previous one, resulting in an amazing environment for the biotech VCs.
The top bio-bet-maker: Robert Nelsen, of Arch Venture Partners. Nelsen has been in the business for two decades and ranks #16 on the list. He was the original venture capitalist behind Illumina , which popularized the use of DNA sequencing in biology and is now a $23 billion (market cap) company. Among the more recent bets that landed him on the list: Juno Therapeutics, the $4.1 billion (market cap) developer of cancer-killing cell therapies; Agios, the $1.5 billion (market cap, again) developer of drugs that mess with tumor metabolism; and Kythera, which developed a treatment for double chins and was sold to Allergan for $2.1 billion.
Despite the double-chin drug, Nelsen is known as one of biotech’s biggest dreamers. Like Juno, which he has said could cure cancer, many of his bets are very big in both financial and medical scale. Recently, he backed a group of former Genentech scientists who want to create drugs for Parkinson’s and Alzheimer’s (the company, Denali, raised $217 million) and made a big investment in an Illumina subsidiary, Grail, that will aim to create a diagnostic test to catch cancer of any type early.
The biggest dreamer in biotech investing is also the best-performing healthcare investor on our list, during a time when healthcare investors did great. Over a thirty-year career, Nelsen has had two dozen companies go public, and was the initial investor on both Illumina, the $23 billion (market cap) giant that popularized DNA sequencing, and Aviron, which created the nose spray flu vaccine. Recent wins have included Kythera, which made a drug to treat double chins and was sold to Allergan for $2 billion, and Juno Therapeutics, which has a $4.1 billion market cap thanks to efforts to train white blood cells to treat cancer. He's making even more big bets: Denali, stocked with $217 million in venture money, aims to take on Parkinson's and Alzheimer's, and Grail, an Illumina spinout, plans to create a single blood test for most types of cancer. Grail will be ARCH's biggest investment ever.
Carl Gordon, of Orbimed Advisors LLC, ranked #20 on the overall Midas List and second in biotech based on bets on Acerta Pharma ( AstraZeneca bought a 55% stake for $4 billion) and hepatitis C company Inhibitex (sold to Bristol-Myers Squibb for $2.5 billion.) Venrock’s Bryan Roberts comes in #48 on the Midas List and third in biotech, thanks in part to Intarcia, Ikaria, and Juno Therapeutics–all rounds he shared with Arch’s Nelsen. Jonathan Silverstein of OrbiMed, the top biotech VC last year, comes in at #63, the fifth biotech investor on our list.
Other bio-VCs who ranked: James Topper of Frazier Healthcare Ventures (#91) and Beth Seidenberg of Kleiner Perkins Caufield & Byers (#98).
To create the Midas List, Forbes ranks VCs on the number and size of exits (either selling company, or having it go public) over the past five years, with a premium on length and depth of involvement in a deal. Only exits above $200 million count, or private rounds worth $400 million or more.
The question for all of these bio-VCs is whether they can keep up this performance as the biotech market turns less favorable. In 2013, a record $7.1 billion was raised from 50 biopharmaceutical IPOs that began trading, according to Bloomberg. In 2014, 81 offerings brought in a total of about $6 billion.
But in 2015, there were just 55 biotech IPOs worth $4.65 billion. August saw two of the top biotech IPOs ever, as Axovant raised $315 million to develop an Alzheimer’s drug and NantKwest, backed by the billionaire Patrick Soon-Shiong, raised $200 million at a $2 billion valuation to develop cells aimed at killing cancer. But Axovant shares now trade 28% below their IPO price, and NantKwest shares are down 65% from theirs.
There is always a market for promising new science. But that market’s a lot tougher than it looked in the summer of 2015.
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76cb283c2371d75f6d4558465f211fe7 | https://www.forbes.com/sites/matthewherper/2016/03/24/bio-maverick-craig-venter-hacks-bacteria-to-have-tiniest-possible-genetic-code/ | After 20 Year Quest, Biologists Create Synthetic Bacteria With No Extra Genes | After 20 Year Quest, Biologists Create Synthetic Bacteria With No Extra Genes
A team lead by the biologist J. Craig Venter has created, in the laboratory, a species of bacteria with a genetic code smaller than any known to exist in nature–basically creating a new organism with a minimal code necessary for life.
“The goal of completely defining what it means to be considered alive has taken a giant step forward,” says Sir Richard Roberts, who won the 1993 Nobel Prize in biology and is now chief scientific officer of New England Biolabs.
JCVI-syn3.0 (Image: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy... [+] Research at the University of California at San Diego)
The new microbe, dubbed JCVI-syn3.0 473 genes. Of these, 149 genes have completely unknown function. Those will become publicly available in a database, Genbank, when the research is published in Science today.
“The entire field of biology has been missing a third of what is essential for life in any given cell,” says Venter, who is chairman of the J. Craig Venter Institute. “As we move up the evolutionary tree we’re probably missing a whole lot more.”
JCVI-syn3.0 also represents a step forward for the field of synthetic biology, which aims to make living things as engineer-able and programmable as the machines of metal and silicon.
“It doesn’t do anything magical rather than live, eat, and self-replicate,” Venter says. But it is, he says, “the first designer organism in history.”
A 20-year quest
How informative syn3.0’s biology will be about other living things remains a big question. So does the usefulness of synthetic biology. Many synthetic biology companies, including Venter’s own Synthetic Genomics, face obstacles as planned commercial applications like pharmaceutical manufacturing and making petroleum alternatives from algae have proved tough to realize.
But what’s undoubted is that the syn3.0 is the culmination of a two-decades-long quest by Venter and two of his top lieutenants, Clyde A. Hutchison III and Hamilton O. Smith, who were both also involved.
“I’d say mission accomplished,” says George M. Church, the Robert Winthrop Professor of Genetics at Harvard Medical School and a synthetic biology pioneer. “It’s not every day that such a big group spends 20 years on something and do what they set out to do.”
J. Craig Venter, Ph.D., Dr. Hamilton O. Smith, M.D., Dan Gibson, Ph.D., Lijie Sun, Ph.D., John... [+] Glass, Ph.D., Krishna Kannan, Ph.D., John Gill, and Dr. Clyde A. Hutchison III, Ph.D. (Image: J. Craig Venter Institute)
A “managerial genius”
The quest to create syn3.0 began 20 years ago, and has been throughout an example of what Roberts calls Venter’s “managerial genius:” his ability to pull together large teams of scientists to accomplish big projects.
In 1995, a team that included Venter, Smith, and Hutchison produced the first genetic sequences of a free-living organism, Haemophilus influenzae, which causes many common childhood infections.
The next step was to sequence the smallest bacteria then known: Mycoplasma genitalium, which has 525 genes, and may or may not be sexually transmitted.
Claire Fraser, director of the Institute for Genome Sciences at the University of Maryland, was the first author on that paper. (She is also Venter’s ex-wife.)
“I find it interesting that the number of genes in JCVI-syn3.0 is essentially the same as what we originally reported for the M. genitalium genome,” she writes via email. She notes that although those estimates were imperfect, “this suggests that we may now better understand the lower limits of the number of genes required for a viable, self-replicating cell.”
Re-booting a bacteria
The idea of such a small, 525-gene genome spurred an idea: What if you could figure out what the minimum genes needed for life were?
There’s probably not a single answer to that question: Even in a tiny bacteria, lots of genes have duplicate functions. There’s more than one minimal genome. But the project began to try to remove some of those genes. It turned out to be tough, and continued as the three went to Celera Genomics, a startup that sequenced the human genome, and then back to Venter’s The Institute for Genomic Research (TIGR) and finally his eponymous institute, which replaced TIGR.
In 2010, the team had a breakthrough: They reconstructed the genome of a different species of Mycoplasma synthetically, outside the bacteria. Then they removed a bacteria’s genome and replaced it with the synthetic one. This allowed them to start creating synthetic genomes which lacked genes. But the first ones, using previous predictions of the minimum number of genes, didn’t boot up. The 473-gene version is the result of repeated attempts to add and remove genes and still have a bacterium that can reproduce itself.
JCVI-syn3.0 (Image: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy... [+] Research at the University of California at San Diego)
What’s it all mean?
Venter expressed hopes that his new little bacteria may provide clues to what early life was like. He notes that the cells changed in size and behavior when genes were removed.
Roberts is skeptical. Bacteria change in dramatic ways when one adds or removes genes. Who’s to say what any change means on an evolutionary scale?
Church has doubts on another front: the idea that editing genomes outside the cell is the best way to accomplish synthetic biology’s goals. He’s been one of the leading scientists developing a technology called CRISPR that allows researchers to edit DNA within living cells. Making lots of edits, he has long insisted, is a better approach than trying to edit genomes as if they were on a word processor. So far, he notes, the genome transplant technique has only been applied in mycoplasma, not in workhorses like Escheria coli, one of the main bacteria used in scientific research. In one instance, a team in Church's lab used these techniques to create an organism dependent on an amino acid not found in nature.
“You’re a writer,” Venter responds. “Can you edit a story on synthetic biology enough to make it a story about the human genome and cancer? You can only get so far with editing.”
Synthetic biology’s slow progress
There’s no doubt that whatever its approach, synthetic biology has gone far more slowly than many researchers hoped. In 2006, the field seemed to be exploding as researchers created cool toys like E. coli that smelled like bananas instead of poop.
In 2007, Venter announced the formation of Synthetic Genomics, which had an initial deal with British Petroleum. In 2009, Exxon announced plans to put as much as $300 million into the company’s work to use genetically modified algae to produce an alternative to petroleum. Church had his own alternative fuel company, LS9, which was eventually merged into another firm.
But efforts to produce fuel from algae ran into problems, especially as the cost of oil kept dropping. “Certainly the biofuel approaches don’t look as promising as when oil is at $200 a barrel, and the more oil goes down the less promising that looks.”
Another big win for the field–making the malaria drug artemisinin in yeast–has also disappointed, as the synthetic biology version of the medicine has not been competitive with traditional methods of making the drug. Nature reported last month that Sanofi , which bought the synthetic yeast, did not use them to make any artemisinin last year.
Venter is still bullish of the field’s long-term prospects. He points to other projects at Synthetic Genomics, including an effort to make omega-3 fatty acids, another to produce protein drugs more efficiently than is possible with 30-year-old technology used by the drug industry, and the production of instrumentation for synthesizing DNA. And, of course, to the giant step forward his team just took in creating a designer organism.
JCVI-syn3.0 (Image: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy... [+] Research at the University of California at San Diego)
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3cbe9c9c016407ea579968522d61967b | https://www.forbes.com/sites/matthewherper/2016/04/01/regenerons-drug-to-ease-terrible-rash-could-be-4-bilion-seller/ | Regeneron's Eczema Data Look Great. Don't Believe Me? Ask A Patient | Regeneron's Eczema Data Look Great. Don't Believe Me? Ask A Patient
Austin Jacobson, a 54-year-old trial attorney, had had rashes since he was a baby. At first they occurred in the warm weather when he played, and would go away with calamine lotion. But after he got married, and then had a child, they got worse. For twenty years, he endured itching that he says was like having poison ivy all over his body all the time.
“It was on every surface of my body with the exception of the palms of my hands and the soles of my feet and, in truth, I looked like a monster,” says Jacobson. “My skin was red, raised, and scaly and I would just literally drop pieces of skin everywhere I went.”
Image courtesy Austin Jacobson
Jacobson is an emergency medical technician with his local fire department, but the chief didn’t want to send him on calls because patients were often terrified they would catch what Jacobson had. He loved to ski with his son, who is now a skilled college skier. But the ski clothing left him covered in bleeding scabs. When playing tennis, tube socks had the same effect. In court, it made him self conscious. He couldn’t sleep, and would wake up with bloody sheets. Sometime, he says, he thought about killing himself, but couldn’t stand the thought of an EMT he knew finding him.
This skin disorder is called atopic dermatitis, the most common form of eczema, a group of diseases of skin inflammation. Now, those suffering from the disease may get relief from a new experimental drug, dupilumab, being developed by Regeneron, a biotechnology company in Tarrytown, N.Y., and Sanofi , a giant drug company based in Paris. Today, the companies released data from two studies that could lead to the drug being made available on the U.S. market.
It is already helping Jacobson. He started taking dupilumab in a clinical trial in October 2014. He has been asymptomatic ever since.
The main measure in the new studies was how doctors rated patients’ disease on a five-point scale from 0 (no rash) to 4 (bad rash). The data are incredibly consistent: Regardless of which study they were in, between 36% and 38% of patients who took dupilumab had their rash drop from a 3 or 4 to a 0 or 1. On placebo, only 8.5% to 10% saw their rash reduced that much.
Patients who received dupilumab improved on another rating scale, the Eczema Area and Severity Index (EASI), about 70% of the time, roughly twice as often as when patients got placebo. Patients who received dupilumab had more redness and swelling of the eye than those who received placebo, although they actually had fewer adverse events overall. The studies tested giving the drug either once a week or once every two weeks; it was not any more effective at the higher dose.
Geoffrey Porges, a biotechnology analyst at the investment bank Leerink, wrote on March 18 that investors would expect an improvement of about 25% or 30% on the five-point scale, and 45% to 55% on the EASI scale, both significantly lower than the drug achieved.
"We all in the dermatology community and in the eczema community we are very excited,” says Emma Guttman, a physician-researcher at Mt. Sinai Hospital in New York and one of Jacobson’s doctors. “We have many patients who have exhausted everything available." Guttman works with Regeneron and Sanofi in conducting clinical trials.
The results could result in a windfall for Regeneron and Sanofi as well. Porges, the Leerink analyst, recently forecast dupilumab sales of $4.3 billion in 2020, at which point the drug will be the best seller for Regeneron, which invented it. The two companies split sales on medicines they co-develop evenly. Porges wrote that a positive result could lead Regeneron shares to increase 7%.
George Yancopoulos, Regeneron’s cofounder and chief scientific officer, says that he views dupilumab as a potential treatment for a wide range of allergy-related conditions. “This really is the deviant pathway that’s driving allergic disease in general,” he says. Clinical trials of the drug in asthma are ongoing, and the medicine will be filed with the Food and Drug Administration later this year in atopic dermatitis.
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4cd2bd974dd246e253495cd3c580abef | https://www.forbes.com/sites/matthewherper/2016/06/05/abbvies-new-lung-cancer-drug-may-extend-patients-lives-but-could-disappoint-investors/ | AbbVie's New Lung Cancer Drug May Extend Patients' Lives, But Could Disappoint Investors | AbbVie's New Lung Cancer Drug May Extend Patients' Lives, But Could Disappoint Investors
An experimental drug may be the first medicine to make a real difference for patients with small cell lung cancer, a particularly deadly tumor that kills 60,000 Americans a year, according to new data presented here at the annual meeting of the American Society of Clinical Oncology. But the results may be disappointing to Wall Street, which already has high expectations for the medicine, known as Rova T.
Investors in AbbVie , the $24 billion (sales) drug giant based in Chicago, are watching closely. AbbVie acquired the cancer drug in April in a blockbuster deal in which it spent $5.8 billion to buy Stemcentrx, a biotech startup backed in part by Facebook billionaire Peter Thiel. AbbVie also promised to pay Stemcentrx investors $4 billion if Stemcentrx’s drugs are approved and hit undisclosed sales thresholds. Ten billion dollars is a heady price for a company that has never been traded on a stock exchange and that, just a year ago, had remained in stealth mode. AbbVie (annual sales: $24 billion) has been getting a reputation as a big spender in the market for cancer drugs, having bought another biotech firm, Pharmacyclics , for $21 billion last March.
AbbVie’s chief scientific officer, Mike Severino, says the company did the expensive deals because it is “uniquely positioned to see the value” in the cancer medicines it has bought. “We think the picture that is starting to emerge around the biology around some of these targets makes this a very, very appealing area for us, and it’s a good fit for our overall skills.”
The Stemcentrx drug, known as rovalpituzumab tesirine but nicknamed Rova T by scientists who couldn’t pronounce that either, targets a protein called DLL3 that is normally found only deep inside cells. But DLL3 winds up all over the outside of some types of cancer cells. Rova T pairs an antibody, which detects DLL3, with a powerful chemotherapy that kills the cells the antibody detects.
Small cell lung cancer kills 60,000 patients a year, and there has been no change in survival rates since the 1970s, according to Charles Rudin, the Memorial Sloan Kettering oncologist who ran the Stemcentrx-funded study. Levels of DLL3 in tumors also don’t predict that patients with small cell cancer will do any better.
That is, unless those patients get Rova T. Then whether tumors express DLL3 starts to matter an awful lot.
Overall, tumors shrank (known as a partial response) in 11 out of 60, or 18% of the patients in the study. Among the 26 patients who had the highest levels of DLL3, 10, or 39%, saw their tumors shrink. In other words, only one patient whose tumor cells weren’t covered with DLL3 benefitted at all.
At the end of a year, 32% of the patients who got Rova T and had high DLL3 levels were alive, compared with 18% for those who tested negative for DLL3. Severino, the AbbVie chief scientist, says that historically only 12% of small cell lung cancer patients who are this sick would be alive at the end of a year. Patients did well whether they had failed one previous course of therapy, or two.
“The group of patients who expresses this biomarker at high level are the ones who are going to benefit from this drug,” says Rudin.
But investors may be expecting even more. Historically, AbbVie has told investors, the median survival for these patients would be expected to be 4.7 months. For the overall trial, the result is 4.6 months. For the high DLL3 expressers, the median survival was 5.8 months. Many on Wall Street are likely to find that 1-month survival benefit disappointing.
The next step will be to test Rova T in a 154-patient study that will only include patients with high DLL3 levels. That study has started and could read out next year, and serve as a basis for an approval from the Food and Drug Administration. The drug will also be tested in small cell patients who are less sick, and in other cancers.
Rova T caused some serious side effects. The most severe included fluid build-up in the heart or lungs, low platelet counts, and skin reactions, all of which happened in about 10% of patients. Some of these patients were receiving a higher dose of Rova T than will be used in future trials.
As for overpaying? Severino says he didn’t. If AbbVie ends up paying out the full $10 billion for Stemcentrx, he says, “it would be a very good deal for us indeed.”
Severino notes that AbbVie gets not only Rova T, but also four other drugs in clinical trials, many more that could start tests soon, and a whole platform for discovering more. Some investors who like the company note another fact: AbbVie, like most other drug companies, keeps much of its cash overseas in order to avoid paying U.S. taxes. "We feel very comfortable here."
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f83d1551a9063ed39612c0b52d0d03a3 | https://www.forbes.com/sites/matthewherper/2016/06/21/team-funded-by-billionaire-sean-parker-aims-to-be-first-to-use-crispr-gene-editing-in-people/ | Team Funded By Billionaire Sean Parker Aims To Be First To Use CRISPR Gene Editing In People | Team Funded By Billionaire Sean Parker Aims To Be First To Use CRISPR Gene Editing In People
Today at 10:40 a.m. Eastern Time, researchers from the University of Pennsylvania will ask a government panel for permission to be the first to use CRISPR, a new type of genetic engineering, to treat a disease in people.
The effort is being funded by The Parker Institute, the new philanthropy created by Facebook billionaire Sean Parker to battle cancer. The CRISPR work builds on earlier efforts by University of Pennsylvania professor Carl June.
The idea, June explained at the Forbes Philanthropy Summit earlier this month, is to make T cells, a type of white blood cell, “better than nature made them.” The cells will be edited to lack several genes, including one that allows them to respond to a protein called PD-1, which acts as an off-switch that some cancers hijack to evade the immune system. (New drugs from Merck , Bristol-Myers Squibb and Roche all target PD-1.) “This is the first example of CRISPR in a clinical trials in humans, period,” Parker said.
As radical as using CRISPR might sound, in this context it is probably not ethically different from any other gene therapy, including the existing work on T cells that has gained June renown and fascinated Parker. “From an ethics perspective, I don’t think it makes any difference,” says Hank Greely, a Stanford lawyer who follows cutting-edge biotech closely. “It’s not anything new, it’s just the normal ethics of trying to do gene therapy.”
Where he does worry, Greely says, is in the area of financial conflicts of interest. Intellectual property could be owned in a complex web between June, Penn and the Parker Institute, although Parker has said his institute will own all resulting intellectual property. What it boils down to is: Could Penn be nicer to the trial because it stands to make a lot of money.
(Photo by Christopher Furlong/Getty Images)
The study, which will also be conducted at M.D. Anderson and Stanford, still has a lot of hurdles to pass. Aside from the government panel–the Recombinant DNA Advisory Committee, which is being webcast here–the study still has to get through investigational review boards at the universities where it will be conducted.
Still, June says that the Parker Institute is allowing the new therapy to move at a speed not permitted by government or industry funding. “Frankly, we’re more nimble than the big pharmas and the big biotechs.”
The new project represents a way around June’s current big pharma partner, Novartis , which licensed technology for using what are called chimeric antigen receptor T-cells, which are programmed using a construct that includes parts taken from a drug antibody. Final trials of these cells for blood cancers are in progress; they could reach the market next year.
Instead, this time the genetic manipulation is being done using a T-cell with a T-cell receptor that attacks cancer. An earlier version of this technology was licensed to Tmunity, a Penn spinout. In conversations with the Parker Institute, it was not clear who would own intellectual property around the new cells, or what that intellectual property would be.
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e222d3ee37b9fb53b82a4361d8651607 | https://www.forbes.com/sites/matthewherper/2016/07/07/juno-therapeutics-stops-trial-of-cancer-killing-cells-after-3-patient-deaths/ | Juno Therapeutics Stops Trial Of Cancer-Killing Cells After 3 Patient Deaths | Juno Therapeutics Stops Trial Of Cancer-Killing Cells After 3 Patient Deaths
Three patients have died in a closely watched study of using genetically engineered white blood cells to treat adult leukemia patients, forcing the trial to be put on hold.
The news is a blow for Juno Therapeutics, the biotechnology startup valued at $4.3 billion that is developing the treatment, known as a chimeric antigen receptor T-cell, or CART. It’s also a blow for the entire field of these cells, which genetically engineer a patient’s own T-cells (a type of white blood cell) so that they will attack the B cells that become malignant in many types of blood cancer. The technique has grabbed headlines because it is daring and because it seems to make cancer disappear, at least temporarily, in patients who have failed other treatments.
Photographer: Victor J. Blue/Bloomberg
The CART in question, JCAR015, is aimed at becoming JUNO’s first product on the market, with data that could support an approval coming as early as next year in adult lymphoblastic leukemia (ALL). Competitors are developing similar products in other types of patients: Novartis in kids with ALL, and Kite Pharma in patients with a type of non-Hodgkin lymphoma.
“This is a humbling experience,” says Hans Bishop, Juno’s chief executive officer. “No doubt it is difficult for the physicians who are looking after these patients and their families. Clearly these therapies are potent, that’s why they offer the potential for cures. We’re still learning to use them in the safest, most efficacious way.”
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It’s too early to say for sure if Juno will be slowed in its path to market. In an interview, Bishop and Juno chief financial officer Steven Harr said that they think they understand why the deaths occurred, that they think they can get the trial back on track quickly, and that they do not think this will affect the development of the other eight CART programs the company is pursuing.
Bishop says that the culprit appears to be a new drug, the chemotherapy fludarabine, that Juno recently added to the trial, called ROCKET. In the CART treatment, patients are first given a chemo cocktail that kills their existing T-cells. This gives the new T-cell, genetically re-engineered to attack cancer, room to grow. Juno has previously presented work showing that adding a drug called fludarabine to the chemotherapy makes the CART cells take root faster. For this reason, JUNO decided to start adding fludarabine to patients partway through.
Except in this study, the combination of fludarabine and the JCAR015 cells seems to have proved lethal. Twenty patients have been enrolled in the study, with as many as 90 planned. Out of those, Harr says, only a minority have been treated with fludarabine. A first death occurred from cerebral edema with a patient treated with fludarabine, but Juno, the outside researchers running the trial, the data safety monitoring board charged with treating patients, and regulators did not think it was related to treatment. But then a second death from cerebral edema occurred last week in a patient who had been treated with fludarabine, leading the trial to be stopped, followed by a third death, also from cerebral edema.
The Food and Drug Administration put a clinical hold on the study, meaning that patients cannot be enrolled in it. In order to lift it, Juno is proposing that it stop using fludarabine with JCAR015. FDA seemed on board with that idea during a conference call yesterday, Bishop says. Instead, patients will be treated only with cytoxan, the drug used in previous trials of JCAR015. In those studies, conducted by Memorial Sloan-Kettering Cancer Center, the drug had a complete response rate of about 80%.
Juno will submit four documents to the FDA as a response to the clinical hold: a modified protocol that does not contain fludarabine; an updated brochure for investigators in the study; an updated patient consent form; and a copy of a presentation used in yesterday’s teleconference with the FDA.
These documents will be submitted by the end of the week. Juno says the FDA indicated it would review the documents quickly. A standard review would take 30 days.
“It is a big deal,” said Otis Brawley, chief medical officer of the American Cancer Society , when told of the halt. But he’s says he’s seen clinical holds resolved in the past, including with important drugs like Taxol. He says the fact that the deaths seem so clearly linked with fludarabine is a good sign. “That actually helps them a little bit. And hopefully they can get this back on track,” Brawley says.
Juno says that it will continue to use fludarabine in trials of its other CART therapies, because the drug seems to make its other treatments, JCAR014 and JCAR017, more effective without this level of toxicity. Other trials of JCAR015, including one in pediatric ALL, are not impacted by the clinical hold. Right now, Juno, Novartis, and Kite have all picked the first indications for their CART treatments. But Harr says Juno’s long-term strategy is to develop the JCAR017 product as a potential best-in-class treatment for all these blood cancers.
“I believe Juno’s got the greatest clinical experience in ALL,” says Bishop. “We’ve treated I think 130 patients with adult and pediatric ALL. And I think to your question about competitiveness, I think the learning that comes from multiple trials and that degree of patient experience I believe is going to be very informative to figuring out the best protocols for using these therapies in these patients.”
Juno’s bet has always been that by developing more types of therapies, and doing more basic science, it can understand a new kind of treatment better than its competitors. It’s a great strategy. But biology is tricky, and medicine unpredictable. Nobody predicted that Juno was going to have to stop its study because patients died. And there’s no way to make that a good thing.
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8c96d06ad6150c351fba15b78d34562c | https://www.forbes.com/sites/matthewherper/2016/07/12/experimental-drug-dramatically-reduces-post-partum-depression-in-small-study/ | Experimental Drug Eliminates Postpartum Depression In 7 Of 10 Patients | Experimental Drug Eliminates Postpartum Depression In 7 Of 10 Patients
An experimental drug led to remission of postpartum depression in 7 of 10 patients, compared to 1 of 11 patients in a placebo group, boosting hope that the medicine might help women who become so distraught after childbirth that they need to be hospitalized.
The drug, SAGE-547, had previously led to an easing of postpartum depression in all four patients in a preliminary study. It is also being studied as a treatment for a rare and severe form of epilepsy. The stock price of its maker, Sage Therapeutics of Cambridge, Mass., rose 37% to $46 in morning trading, giving the company a market capitalization of $1.5 billion. Harry Tracy, author of the investor newsletter Neuroperspective, says the market for such a postpartum depression drug could be 200,000 to 600,000 patients annually.
SAGE-547 must be given intravenously, and the market for this medicine will be women whose depression is so severe they are hospitalized. The drug is a synthetic version of a hormone, allopregnanolone, that is thought to drop precipitously after childbirth, triggering postpartum depression.
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“The difference between this and something else that has too-good-to-believe results is the pharmacology is probable,” says Jeffrey Lieberman, the Lawrence C. Kolb Professor and Chairman, Department of Psychiatry, Columbia University College of Physicians and Surgeons. “I would say it’s exciting, but I certainly wouldn’t say this is definitive or a slam-dunk finding.”
Sage’s chief executive, Jeff Jonas, had previously said the goal of the study was to show an effect that is much bigger than that for antidepressants. It did that. On the 29-point Hamilton depression scale, patients who received SAGE-547 had a reduction of 12 points more than placebo, or about 22 points. Traditional antidepressants yield reductions of about 4 points less than placebo.
Sage Therapeutics CEO Jeff Jonas
But depression results can become far less positive as studies become larger. For reasons that are not entirely clear, the magnitude of benefit can become smaller for treatments, and placebo effects can become larger. Most recently, a treatment for severe depression developed by Alkermes that had shown promise in severe depression failed to confirm its benefit in larger trials.
Jonas says that he believes that carefully defining who gets the drug and making sure the medicine has a big effect can help assure the benefit won’t get washed out by an inflated placebo effect.
There’s a lot of work to be done. Jonas says the study “is not big enough” to result in an FDA filing. He wants to start a larger study to confirm that SAGE is using the right dose of SAGE-547 for postpartum depression. The company needs to meet with the Food and Drug Administration to determine what types of studies will need to be run in order to get the drug approved. One risk is that he does see the company moving into slightly less severely depressed, though still hospitalized, patients.
After that, there are bigger questions. Can Sage develop oral drugs that will be as effective as SAGE-547? The company has another medicine, SAGE-217, that Jonas says he’s pushing to get into trials. Even more important: Does the biology around these medicines work in other kinds of depression, or just in postpartum? Are these different diseases?
“What we know today is we have this big effect size in [postpartum depression], and that is going to be our focus,” Jonas says. But says it is “incumbent” on Sage to explore other forms of depression, too.
The story says something about the start-and-stop nature of drug development. The work that led to these drugs started three decades ago. Some of it was done by Steven Paul, a research scientist who went on to run drug research at pharmaceutical Eli Lilly for 17 years. It was only after the Lilly job ended that he helped found Sage.
“If this turns out to be a novel and highly effective new way of treating depression, it will have derived from work that was done over three decades earlier and then meandered until was operationalized by a small startup company,” Lieberman says. And now, all of a sudden, it is moving at a breakneck pace.
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46e782750e08cbc25299d3c4b74e9550 | https://www.forbes.com/sites/matthewherper/2016/09/20/approving-a-muscular-dystrophy-drug-ignites-civil-war-at-the-fda/ | Approving A Muscular Dystrophy Drug Ignites A Civil War At The FDA | Approving A Muscular Dystrophy Drug Ignites A Civil War At The FDA
Yesterday, the Food and Drug Administration made history, approving a drug to treat Duchenne muscular dystrophy that works by targeting the genetic mutation at the root of the disease.
The decision was unique for reasons that were not just scientific. Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, overruled the protests of her own staff to approve the drug. One of her division’s top officials appealed the ruling, and the agency’s chief scientist largely backed his conclusions, saying that “by any meaningful objective standard” the medicine is unlikely to improve patients. But the FDA’s commissioner, Robert Califf, decided not to overturn Woodcock’s decision, citing Woodcock’s long record of independence and arguing that her differences with other FDA scientists were a matter of honest scientific disagreement, and the decision was within Woodcock's authority.
In this Friday, June 5, 2015 photo, 10-year-old Gabe Griffin sits in a train on a playground in... [+] Birmingham, Ala. Griffin suffers from Duchenne muscular dystrophy, a rare muscular degenerative disease that gradually and then rapidly leads to incapacitation before ultimately to an early death. (AP Photo/Brynn Anderson)
The news is an unmitigated win for Sarepta Therapeutics, the biotechnology company that developed the drug, now known as Exondys 51 or, generically, eteplirsen. Sarepta shares increased 74% to almost $49, giving the company a market capitalization of $2.5 billion. Last night, on a conference call with investors, the company said that it expected to charge $300,000 per patient per year for Exondys 51, with the exact dosage being determined by weight. The company, which might have folded with a rejection, will now have money to fully test Exondys and other, similar drugs for Duchenne.
For patients with Duchenne, the approval is also a victory. Patient advocates campaigned hard for Exondys to be approved, with many attending an expert panel the FDA convened in April. At the time, the outside experts convened by the FDA voted 7-6 to recommend the FDA should not approve Exondys.
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“The moment I saw eteplirsen received approval, I broke down, I cried,” says Josh Argall, a network technician whose 15-year-old son has Duchenne caused by the gene Exondys 51 targets. “When my son was diagnosed 12 years ago a lot went through my mind that I wouldn’t be able to do with him. I felt as though some of our future was taken away. Today, it was given back and man, I couldn’t be more thankful.”
But for the FDA, the decision represents a civil war that could have unknown reverberations. Ronald Farkas, the FDA reviewer charged with reviewing the Exondys new drug application, has already left the agency to take a job in industry. The contention between Woodcock and Ellis Unger, who is in charge of reviews of heart, kidney, neurology and psychiatric drugs, are sharp.
And some outside experts are already arguing that Unger was right. Eric Topol, chief academic officer at Scripps Research Institute in La Jolla, Calif., says the decision is “compromising reasonable approval standards.” Walid Gellad, an associate professor of medicine at the University of Pittsburgh who frequently serves on FDA panels tweeted: “Let me summarize: a drug the FDA says has no clinical benefit will cost four times as much as a drug that cures hepatitis C.”
The approval of Exondys is called an accelerated approval, meaning that the FDA has the option of withdrawing it if specific future studies don’t prove out the drug’s benefit. Topol says he wishes that Congress had instead created a conditional approval, where the drug would be automatically withdrawn unless studies show it really works.
From the start, the Sarepta story has been a strange case. It was incredibly expensive to make–in small batches probably costing $100,000 per patient, analysts say–and the company was strapped for cash. So it did a small study of 14 patients. Two of those patients were not evaluable, but in the rest something surprising seemed to happen: those that got Exondys 51 from the start of the study seemed to do much better than those who had a delayed start on the drug. More enticingly, the boys (because the genetic defect that causes Duchenne is on the X chromosome, it is a disease of boys) seemed to be showing marked increases in dystrophin, the protein that is missing in the disease.
Based on these results, Sarepta filed with the FDA. It was likely the smallest pivotal study in FDA’s modern history. The FDA now says that it implored Sarepta to run a placebo-controlled study with more patients, but the company argued that it would be impossible to get Duchenne patients to enroll given the already positive results. But the FDA’s reviewers–in particular Farkas--did not believe the study results. They said the differences between boys who got the drug at the beginning of the trial and those that had to wait could be due to chance, as could what advocates said was the overall tendency of all the boys to do better than expected.
Worse, the FDA had issues with the way Sarepta had tested dystrophin. After the FDA’s April advisory committee voted that the drug should not be approved, the FDA and Sarepta agreed to look at one more set of data points: Samples would be taken from patients to see if their dystrophin levels increased after 48 weeks of treatment. It was possible to get data from 12 of those patients. When the dystrophin data were produced the FDA would make a decision within four days, per an agreement made by Woodcock and agreed to by Unger.
But when the data came in on June 27, they disappointed even Woodcock, according to a review of the facts presented by Luciana Borio, the FDA’s Acting Chief Scientist. The data showed an increase of only 0.28% of normal levels, which was, on average, a tripling of dystrophin levels for these boys. But Unger and the reviewers argued that, based on comparisons of different types of muscular dystrophy, an increase beyond 10% of normal would be needed to have a clinical impact on muscular dystrophy symptoms.
Unger wanted to ask Sarepta to test the current dose of Exondys 51 against a much more frequent dose of the drug before approving the medicine. If the more frequent dose was more effective, the drug could then be approved. Woodcock, despite the disappointing data, wanted to grant accelerated approval right away.
“By allowing the marketing of an ineffective drug, essentially a scientifically elegant placebo, thousands of patients and their families would be given false hope in exchange for hardship and risk,” Unger wrote in his protest. “I argue that this would be unethical and counterproductive. There could also be significant and unjustified financial costs–if not to patients, to society.”
The FDA is not supposed to concern itself with the cost of a drug. But both Unger and Woodcock were. Unger was worried about the unknown risks of the drug, as well as the risks to boys who might get injection ports while they were also on immune-suppressing steroids, raising the risk of infection. Woodcock was worried about the cost to Sarepta.
Woodcock, according to Borio, argued that if the drug were not approved, Sarepta would see its stock price crash and probably go out of business. It was probably true. Brian Skorney at R.W. Baird, an analyst who has gotten the Sarepta story very much right, estimates Sarepta would have needed $400 million to complete the study, yet would have had only a $250 million market cap on rejection–meaning it couldn’t raise the money it needed if the FDA rejected it. It’s also not a reason to approve a drug.
At the end of the day, Woodcock, Unger, Borio and Califf all wound up agreeing on many key points: that Sarepta’s studies were flawed and difficult to interpret; that early versions of the Sarepta data as released were misleading; that both the FDA and Sarepta stumbled at multiple points along the way; and that, at the end of the day, Sarepta’s drug showed only a minimal amount of dystrophin was produced. The disagreement is on one point: was this tiny increase in dystrophin enough to merit approving the drug, even on a conditional basis?
Woodcock decided the answer was yes, and, for the first time in her eight-and-a-half-year term as director of the FDA’s drug division, overruled her scientists and decided to approve the drug, saying that she wanted to use “the greatest flexibility possible for FDA while remaining within its statutory framework.”
Borio, the FDA’s Acting Chief Scientist, sided with Unger. “By any meaningful objective standard, however, the overall evidence derived from eteplirsen’s limited clinical development program does not support that the levels of dystrophin produced by eteplirsen at the doses studied are reasonably likely to provide a clinical benefit.”
But the final decision sat with Robert Califf, the FDA Commissioner who, as an academic researcher, made a career of pushing companies to do bigger, more rigorous data. At the end of the day, he declined to make his own judgment on the merits of Sarepta’s data. He simply decided that Woodcock had not overstepped her authority and that he, a political appointee, was not going to take another gigantic step by overruling the FDA staff.
Califf’s memo asserts that this decision should not be seen as precedent. But it will. Companies will spend more on lobbying, and more on supporting patient groups as a result. They will also try to push through drugs with minimal data. The decision also will demoralize FDA staff--imagine being told your boss could push you around even more. It would have been better if he had grappled with the data instead of throwing up his hands and standing on procedure.
Those who fear that the FDA has been lowering the bar dramatically in recent years will hate the Exondys approval. One critic told me: “This isn’t even science!” The FDA has approved a drug, essentially, on a minimal efficacy data from 12 patients and safety data from a larger dataset. But this was always a tough decision, because this was exactly the kind of case that accelerated approval was designed for: A death sentence with no options. It’s wrong for the FDA to approve a drug without evidence it works, but it’s also paternalistic to say boys with Duchenne and their families shouldn’t be able to take risks they dearly want to take.
At least this decision sets up a clear path for testing whether Exondys works: A more frequent dose (the FDA suggests daily dosing) should clearly outperform the currently approved dose, or the FDA will yank the drug. The agency, after taking such a big risk, will have to follow through on yanking the drug if that trial, due in 2020, is not positive. That gives Sarepta, or whoever buys it, three years to marshal its evidence.
The lobbying floodgates were already opened by a far worse decision: The FDA’s approval of Addyi, a drug to treat female sexual dysfunction that had little evidence of efficacy. Its maker, Sprout Pharmaceuticals, created a campaign that presented the approval of the drug as a feminist issue, and the drug got approved. That’s a far cry from giving a shot at a longer life to dying boys.
But Exondys should represent the absolute minimum in terms of the data required to get a new medicine to market. And in the future, we need to find ways to communicate the FDA’s concerns about an experimental medicine to the public, not just to a drugmaker behind closed doors.
And Congress should now stop mucking with the FDA approval process for a while. In an effort to speed up the bureaucracy, legislators have layered breakthrough designations on priority reviews on fast tracks (all seek to declare some drug reviews special), while adding vouchers and other measures aimed to incentivize drug development. In addition to the hundreds of millions in annual sales Sarepta will get for selling its $300,000 drug, it will also get a priority review voucher for developing a rare pediatric drug. This is a coupon forcing the FDA to speed up review of a drug that’s not innovative. The last such voucher netted $330 million in an auction. Given that the FDA brass all agreed Sarepta had touted study results that were misleading, does the company really deserve what's essentially an extra year of sales?
Legislation under consideration aims to add more such incentives. It’s time to put on the brakes. There’s no argument now: the FDA is bending over backward to make sure that patients have access to medicines, using the maximum flexibility of the law. In an agency driven by precedent, this decision will matter. Already, medicines are usually approved in America before they’re approved anywhere else. It’s time to pause before the bar is lowered any further.
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b188d12029ccc7a9d5e5a48b6f53345a | https://www.forbes.com/sites/matthewherper/2016/10/04/death-kickbacks-and-a-billionaire-the-story-of-a-dangerous-opioid/ | An Opioid Spray Showered Billionaire John Kapoor In Riches. Now He's Feeling The Pain | An Opioid Spray Showered Billionaire John Kapoor In Riches. Now He's Feeling The Pain
By Matthew Herper and Michela Tindera
On Mar. 25, 2016 Sarah Fuller, 32, was supposed to drop her mother's car at the shop. Her mom called at 8 a.m. to make sure her daughter was up. She got Sarah's fiancé. He found Sarah in her room, motionless, with her face on the floor. She was dead. The medical examiner implicated two drugs Sarah had been prescribed: Xanax, for anxiety, and Subsys, the fastest-acting form of fentanyl, among the most potent narcotics known to medicine. The combination was dangerous, but Sarah's family blames Subsys and its maker, Insys Therapeutics, for her death and plans to sue. "They obviously had no regard for human life," says Debbie Fuller, Sarah's mother. "In order for them to make the bottom line bigger, people have to die for it."
Subsys is the brainchild of John Kapoor, 73, one of the most successful pharmaceutical entrepreneurs in America and the founder, chairman and chief executive of Insys. Kapoor is worth $2.1 billion, and his Insys shares represent $650 million of his net worth. The company's stock is up 296% since its 2013 IPO.
His idea for what became Subsys was to pair fentanyl, a narcotic 80 times more potent than morphine, with spray technology that would allow patients to get a dose under their tongues. The point was to ease cancer-related pain, which often breaks through high doses of existing opioids. It's a subject Kapoor knows well: Editha, his wife of three decades, died of metastatic breast cancer in 2005.
"I was a caregiver for her," Kapoor says. "I took care of her. I saw what she had to go through, and I can tell you, pain is such a misunderstood thing for cancer patients. Nobody understands pain. They think pain is just pain. My wife went through it."
But critics allege that Insys sales reached $331 million last year because the drug is also being used for patients who do not have cancer. Like Sarah Fuller. She suffered from back and neck injuries from two car accidents a decade ago and from fibromyalgia, a mysterious disorder that causes diffuse muscle and bone pain. Kapoor is quick to say that it "doesn't make sense" to give a fibromyalgia patient Subsys, a drug designed to relieve sudden spikes of excruciating pain. (Insys did not comment directly on Fuller's death.) More than that, it would be illegal for Insys to promote the drug for such use, because the Food & Drug Administration has approved Subsys only for cancer patients.
Yet in 2015 a nurse practitioner in Connecticut pleaded guilty to violating a federal antikickback statute by taking money from Insys to prescribe the drug to Medicare patients who did not have cancer. A former Insys sales representative in Alabama also pleaded guilty to a conspiracy to violate the antikickback statute by paying two doctors to prescribe the drug. Illinois has filed claims against Insys related to pushing Subsys for unapproved uses. U.S. attorneys in two jurisdictions--the Central District of California and the District of Massachusetts--are investigating the company. Doctors who have worked with the company are being investigated by Michigan, Florida, Kansas, New Hampshire, Rhode Island and New York.
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One case has been settled: Insys paid the state of Oregon $1.1 million, a small amount for the company but twice its entire book of business in the state, to settle charges that it was working to persuade doctors to prescribe Subsys to patients who did not have cancer. To date, Insys has admitted no wrongdoing and says it has strengthened its procedures to prevent lapses from occurring in the future.
It's familiar territory for Kapoor. He has made a habit of founding companies and allowing them to push legal and ethical limits, confident of his ability to clean up the resulting mess. Insys is just the latest chapter.
"My involvement is I am an investor," Kapoor says. "As an investor I'm on a board. As a board member and an investor you are involved, but you are not involved in day-to-day operations, and that's where the problems come in."
KAPOOR GREW UP MODESTLY in India. He was the first in his family to attend college. He earned a doctorate in medicinal chemistry from the State University of New York at Buffalo in 1972 and quickly went to work in the corporate world. "In India they teach you how to work in a factory," he says. "They don't teach you how to work in a drugstore."
In the 1970s many companies had small divisions that made generic drugs. Kapoor started at Invenex Laboratories, in Grand Island, N.Y., which was owned by Mogul Corp., a water treatment firm. He worked there for six years (he met his wife there), but he wanted to run something on his own. In 1978, he says, he approached LyphoMed, a drugmaker owned by a Chicago corrugated-cardboard maker called Stone Container. Then 35, he not only negotiated a job at the company but also an option to buy it should Stone exit the pharma business.
At LyphoMed he demonstrated a talent for marketing straight out of Mad Men. One of the company's major products was the formula used to tube-feed hospital patients. LyphoMed's product contained vitamins and electrolytes, or micronutrients, and Kapoor seized on the term "micronutrients" as a hook to get his salespeople into otherwise uninterested hospitals. "I always believed in marketing," Kapoor says. "You might have a great thing--but if you don't know how to market, then you can't succeed."
In 1981 Kapoor pulled together a syndicate of investors to help him buy LyphoMed from Stone Container for $2.7 million (about $6.7 million in today's money). Kapoor took LyphoMed public in 1983. Sales boomed as Congress passed laws favoring generic medications. From 1983 to 1989 LyphoMed's sales increased from $19 million to $159 million.
When Kapoor tells this story, however, he leaves out a key part: his near-constant battles with the FDA. LyphoMed's drugs were not produced in a sterile environment, the agency alleged: There was broken glass in what was supposed to be a sterile room. In 1987 and 1988 LyphoMed recalled hundreds of thousands of vials of various drugs, eventually entering a consent decree with the FDA to fix the problems. The FDA reported that the resulting shortage of vitamin B1 for tube-feeding resulted in three patient deaths. In 1990 a congressional subcommittee called LyphoMed's manufacturing problems "legendary."
Kapoor found a buyer, anyway: In 1990 Fujisawa Pharmaceutical, a Japanese drug giant, bought LyphoMed in a deal that valued the company at almost $1 billion. Kapoor personally pocketed $100 million after taxes.
In 1992 Fujisawa sued Kapoor for that entire $100 million, saying LyphoMed's FDA problems were worse than it had been led to believe. He called the charges "preposterous" and settled for an undisclosed (but smaller) amount in 1999. "I don't know how much you know about Japan, but to them, face-saving is very important," he says. "Their way of face-saving was saying: 'John did this.' "
The $100 million fortune allowed Kapoor to spread out his bets. He would found or take controlling stakes in multiple companies at once, and assume the chief executive role only when something went wrong. "In my career my plan has always been: I am the last guy standing," Kapoor says. "I've always taken the company to the finish line. If something happens, I just don't run away and say, 'Okay, I'm done.' I say, 'Okay, I have a big stake in it, and I know the strategy,' and so on a temporary basis I step in and try to see what needs to be done."
Consider Akorn, a Lake Forest, Ill. generic-drug company that accounts for the biggest share of Kapoor's net worth. Over the past ten years Akorn's shares are up 728%, and Kapoor's 26% stake in the company is worth $890 million. But it came close to being worth nothing.
Kapoor invested in Akorn in 1991, as the company grew through mergers with several other firms. In 1996 he became chief executive amid what he remembers as concerns about the company's accounting. He stepped down two years later. He was back as CEO in 2001 as another set of accounting mistakes occurred. The FDA was also investigating problems at the company's plant in Decatur, Ill., which were eventually resolved. Kapoor stepped down again at the end of 2002.
In 2007 the FDA warned of more manufacturing problems, some of which had persisted since 2004. Debts piled up. In 2009 Akorn's annual report said there was substantial doubt about its ability to continue as a going concern. The share price fell as low as 75 cents.
Akorn didn't turn around until Kapoor brought in another new chief executive, Raj Rai, in 2009. Rai had previously run another Kapoor company, a pharmacy called Option Care, which was sold to Walgreens in 2007 for $850 million, including debt. Rai focused Akorn on its core businesses, eye drugs and sterile injectable medicines for hospitals, jettisoning low-margin businesses, including vaccines. Akorn shares now trade at $27, a longtime disaster that turned into a huge win.
IT WAS AT A COMPANY CALLED Sciele Pharma, originally called First Horizon, that the stage was set for Insys Therapeutics and its aggressive marketing of a powerful narcotic. Kapoor cofounded the company in 1992, linking up with an experienced drug marketer, Patrick Fourteau, who had previously run a contract sales force that pharma giants could quickly hire when they needed extra help. Sciele sold heart, pediatric and allergy drugs. Its biggest product was a blood-pressure pill.
Instead of hiring experienced pharmaceutical salespeople, Fourteau hired recent college graduates, nurses and other health-care professionals, paying them low salaries but giving them big bonuses if they got doctors to prescribe Sciele's drugs. Fourteau felt this was better for a small drugmaker. "The big pharma guys--especially in sales--that we recruited were the rejects of big pharma," he says. "When they came to a small company, they thought they owned the world, and they were telling management how to run the show."
When they were just selling blood-pressure pills, this strategy worked admirably. In 2008 Sciele was bought by the Japanese drug giant Shionogi for $1.42 billion. By that time Kapoor had already sold his shares and stepped down from the board.
Read More: Billionaires' Secrets to Building Wealth
At Sciele he'd become fascinated by another of its products: a spray form of nitroglycerin used by heart patients to stop attacks of chest pain. "Patients loved it," Kapoor says. "I started looking into the sprays, and to my surprise, I found it was the only product that was sold as a spray in this country." What other drug would work well as a spray? Well, fentanyl, which cancer patients needed for rapid relief of pain. The idea wasn't a fit for Sciele, so Kapoor brought it to Insys, a small company he'd founded in 2002. Fourteau joined the board in 2011, and Insys decided on a sales-force strategy much like Sciele's, with young, aggressive salespeople. Asking them to sell a potentially deadly narcotic on an incentive plan created a powder keg primed to explode.
THE MARKET FOR PRESCRIPTION opioids is lucrative but fraught with ethical problems. A marketing push by Purdue Pharma in the 1990s resulted in its OxyContin becoming widely used--and abused. Since 1999 the number of prescriptions for opioid pills has quadrupled. The number of annual overdose deaths has quadrupled, too, to 19,000 per year.
Kapoor points out that his drug, Subsys, is but a drop in this flood. Superpotent forms of fentanyl meant for cancer patients are prescribed only 130,000 times a year, Insys says, compared to 200 million for opioids as a whole. (It's difficult to say how many people use the drugs, since patients get multiple prescriptions.) These drugs relieve severe pain, but they come with their own legal problems. In 2008 Cephalon, a Frazer, Pa. drugmaker, paid $425 million and pleaded guilty to criminal charges involving drugs such as Actiq, a fentanyl lollipop. The Department of Justice alleged Cephalon had promoted Actiq, meant only for cancer patients, for a wide range of uses, including pain associated with migraines, sickle-cell anemia and changing wound dressings. Worse, prosecutors said Cephalon pushed the high-dose narcotic to patients who had not previously developed a tolerance to opioids and might have died from their first exposure to such a potent dose of fentanyl. Despite the penalties, Cephalon more than survived: Teva Pharmaceuticals, based in Israel, bought it in 2011 for $6.8 billion.
To navigate this treacherous legal and ethical territory, Insys' board, led by Kapoor, picked as chief executive a man in his mid-30s with little pharmaceutical experience named Michael Babich, whom Kapoor had originally recruited from Northern Trust, a wealth management firm, to work in his family office. Babich, in turn, chose Alec Burlakoff, who had marketed similar narcotics for Cephalon and had been mentioned in a case alleging off-label marketing, to head the sales force. Both have since left the company and did not return repeated calls for comment.
"I think what happened with Insys is that we grew very rapidly," Kapoor says. "We have over 500 employees. I think a lot of things in a business, any business, especially when you have a fast-growing company, you're in a very dynamic situation. Every day there is some decision that needs to be made. Mike did a good job. Yeah, we have some issues with DOJ. But I think, operationally, I felt that Mike may not be able to handle that with so many things happening."
One way drug companies promote medicines is by paying doctors to give talks. This rewards doctors who like a company's products and helps create new converts. In 2015 Insys paid doctors $6.3 million for activities that included speaking, according to data collected by the Centers for Medicare & Medicaid Services. Four doctors received fees of over $100,000, and 11 more received at least $75,000.
Speaking fees aren't illegal unless they are used as bribes for prescribing drugs for unapproved uses. That may have happened. Heather Alfonso, a nurse practitioner in Connecticut, pleaded guilty to charges of federal antikickback laws in June 2015. Prosecutors alleged that she had received speaking payments of $83,000 and prescribed $1.6 million worth of Subsys, largely to patients who did not have cancer. (She worked at a pain and headache center.) She did not contest allegations by prosecutors that, in many cases, she was paid merely to go to dinner with a few people.
In February 2016 a former Insys sales representative, Natalie Reed Perhacs, pleaded guilty to conspiracy to violate antikickback statutes. Alabama prosecutors alleged she'd been hired because a doctor who prescribed Subsys "developed a certain affection" for her and that she arranged speaking fees for him and a colleague in return for their prescribing Subsys. Prosecutors claim she made more than $700,000 between April 2013 and May 2015, despite having a base salary of only $40,000 a year. Neither Alfonso nor Perhacs has been sentenced; neither has commented for this story.
The allegations made by civil prosecutors in Oregon and Illinois mirror the picture created by the guilty pleas, documented with e-mails and text messages from Insys employees. The Illinois complaint alleges that Insys paid $84,400 to one doctor for 46 talks even though the company knew he had been indicted on federal false-claims charges. According to the complaint, an Insys sales rep e-mailed his supervisor and Babich, the CEO, saying that the doctor "runs a very shady pill mill and only accepts cash." Later on the same salesperson sent a message to a supervisor saying the doctor's Illinois office was being watched by the Drug Enforcement Administration but that he was planning to start prescribing Subsys from another office in Indiana. The supervisor responded by saying the doctor would become the salesperson's "go-to physician" and advising: "Stick with him."
In another case, Oregon civil prosecutors allege, Insys hired the son of a physical medicine and rehabilitation doctor as a salesperson. (Their full names are redacted.) The son told his bosses--and later swore under oath--that his father did not treat any cancer patients. But the pressure from Insys to get him to prescribe Subsys, which was approved only for cancer, wouldn't stop. The company paid another physician $1,600 to have dinner with him to try to persuade him to write Subsys prescriptions. And they kept pressuring the son. "This company really wants to make you a speaker," the son wrote to his father. "Apparently Kapoor had good things to say about you. The VP of sales wants to come out and speak with you. I apologize for being pushy."
The Southern Investigative Reporting Foundation, a nonprofit focused on investigative reporting, obtained a recording in which Insys employees seemed to discuss getting insurers to pay for Subsys for patients who don't have cancer.
Babich stepped down in November 2015, and Kapoor took over, as he has done so often when his companies get into trouble. Kapoor has already announced that he is looking for a replacement. His main defense, over three hours of interviews, is naiveté.
"I look at doctors and we think, professionally they're all ethical and all that," Kapoor says. "I learned that in certain areas, like in pain management or in opioids--this is public information, I'm not making it up--that there are doctors that overprescribe and things like that." On speaker programs: "We have very strict company policies," Kapoor says. "If something happened in the field, sometimes the company may not know about it."
It's hard to believe that someone could run pharmaceutical companies for almost 40 years without realizing some doctors overprescribe medicines, particularly pain medicines. Kapoor--and Insys shareholders--would like to move the focus past Subsys, hoping sales, which have dropped in the wake of bad press and government investigations, stabilize. He would like the focus to be on other drugs. Insys just received FDA approval for a synthetic version of THC, the compound in marijuana, to treat nausea. It is developing a spray version of naloxone, the lifesaving antidote for opioid overdoses, and a synthetic version of cannabidiol, a component of marijuana that has shown promise in preventing seizures. Maybe after things with the Department of Justice are finally settled, that will be possible.
Maybe it will be possible after Kapoor steps down. Other small drugmakers have made big ethical missteps and moved on. But the problem with (allegedly) pushing a narcotic for unapproved uses is this: Even after you stop, the consequences are painful.
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1759fc0426febdf3772cdc6c143f101c | https://www.forbes.com/sites/matthewherper/2016/10/26/epipen-competitor-auvi-q-to-return-to-market-promising-lower-costs-for-patients/ | EpiPen Competitor Auvi-Q To Return To Market, Promising Lower Costs For Patients | EpiPen Competitor Auvi-Q To Return To Market, Promising Lower Costs For Patients
Eric and Evan Edwards, the twin brothers who invented the Auvi-Q device. (Image via Kaleo)
The main competitor to the EpiPen will be sold again in the first half of next year, its maker says. Like EpiPen, the shot, called Auvi-Q, can deliver a lifesaving jolt of the drug epinephrine to stop a severe allergic reaction. It was removed from the market last year because of manufacturing problems.
Auvi-Q’s maker, a closely held pharmaceutical company called Kaleo, based in Richmond, Va., promises that Auvi-Q will have low out-of-pocket costs for patients. EpiPen's maker, Mylan, has faced a massive backlash over its price increases. But Kaleo is currently offering no details on its pricing strategy.
“It is not in the best interest of patients or physicians to have high out-of-pocket costs,” says Spencer Williamson, Kaleo’s president and chief executive. “We’re engaging with all of the stakeholders–wholesalers and pharmacy benefits managers--to insure that we can provide this innovative technology to patients and that they can afford it. And we are going to assure that the out-of-pocket is going to be low for patients.”
Williamson says Kaleo will offer Auvi-Q at an affordable price even to patients without health insurance, and promises that competition will benefit patients. In the past, that wasn't true, at least when it came to costs.
Auvi-Q was launched in 2013, by the drug giant Sanofi, which had licensed it from Kaleo, which was then known as Intelliject. The product had some compelling selling points. Auvi-Q is smaller and easier to carry–the size of a credit card, and the thickness of a cell phone. Unlike EpiPen, patients never actually see its retractable needle. And the Auvi-Q instructs users how to give an injected with recorded voice messages, something that could be an advantage when a panicked parent is trying to save a child.
But those advantages didn’t amount to much in the way of sales. In 2015, the Auvi-Q's best year, Auvi-Q was prescribed 353,589 times, compared to 3.4 million prescriptions for EpiPen.
EpiPen’s maker, Mylan Pharmaceuticals, has been widely criticized for raising the price of the EpiPen device by more than 600%. But when Auvi-Q was sold by Sanofi, it took virtually the same increases in its list price as EpiPen. Between 2013 and 2015, the list prices of both products doubled to $500. Mylan has blamed its list price increases partly on a system of wholesalers and pharmacy benefit management companies that are paid rebates in order to stock the drug. Williamson couldn’t clarify how Auvi-Q would now be able to compete on price, saying only that he's working with those stakeholders to come up with a pricing solution.
Sanofi voluntarily withdrew Auvi-Q in October 2015 because in rare cases the syringe would not deliver the proper amount of epinephrine, the drug used to treat severe allergic reactions. Kaleo says it has fixed those problems with an extensive new, automated manufacturing process that uses a production line composed entirely of robots with more than 100 quality checks.
Competition didn't slow EpiPen's price hikes. (Design: Nick DeSantis, Forbes staff)
Auvi-Q was invented by Evan and Eric Edwards, twin brothers who, as children, suffered from severe allergies to eggs, shellfish and nuts. Evan became an engineer, and Eric a doctor, and together they decided to create a device that would be better than existing epinephrine auto-injectors like EpiPen. Now that device is getting a second chance.
“This is personal for us,” says Eric Edwards, who is a vice president at Kaleo. “I’m a patient who may have to respond with this product not only for myself but for my child, and we are committed to making sure that Auvi-Q is going to work during an allergic emergency.”
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9242c82b8de95e652d372c53df281432 | https://www.forbes.com/sites/matthewherper/2016/12/14/should-big-data-pick-your-next-doctor/ | Should Big Data Pick Your Next Doctor? | Should Big Data Pick Your Next Doctor?
Grand Rounds CEO and co-founder Owen Tripp. Credit: Tim Pannell for Forbes.
This past spring, Owen Tripp, 37, was living the Silicon Valley dream. His latest company, Grand Rounds, had raised $100 million at a valuation said to be about $1 billion. He and his wife had a new baby, their third child. Sure, the noise from the kids--all of them under 6--meant he slept with earplugs, but so what? Life was great.
Then he woke up one morning convinced he'd left an earplug in his right ear. He checked. No plug. But he couldn't hear anything in that ear. His doctor twice said it was just clogged before recommending an ear, nose and throat specialist. When he pulled up the specialist's Web page, something didn't feel right: Her expertise was in swallowing, not hearing. "I'm not feeling super-comfortable with the way this is being looked at," he remembers thinking. "Why am I being referred to somebody who seems to be more versed in swallowing?"
Most people would just go to that doctor anyway. Or they'd call friends in the hope that someone would know a specialist. But Tripp is not most people: He is the cofounder of Grand Rounds, which is focused on matching patients with the right doctors. The company uses a database of some 700,000 physicians, 96% of the U.S. total, and merges it with insurance-claims data and biographical information to grade doctors based on the quality of their work. The idea is to help people find a physician who will give them the right diagnosis the first time around and link patients with experts who can give second opinions. For individuals, it costs $600 to get a doctor recommendation and $7,500 to get a second opinion.
Grand Rounds won't provide revenue figures, but employers, including Comcast, Quest Diagnostics, SC Johnson, Wal-Mart, News Corp. and Jamba Juice, pay for the service on a per-employee basis because they believe it cuts down on incorrect diagnoses and unnecessary procedures. Some 3 million employees have access to the service, although only a small percentage use it. At Costco, for instance, 2% of employees used Grand Rounds this year and 60% of those who got a second opinion had their care changed.
The team at Grand Rounds matched Tripp with a doctor in San Francisco. She prescribed a specialized MRI. After the scan, the head radiologist at Stanford called and told Tripp there was a 2.6-centimeter growth--a tumor called a schwannoma--in the nerve that led to his ear.
"My wife is sitting right next to me, and we both start panicking," Tripp says. "I mean, we're cool under fire, but inside we're wondering, How's this going to work for the kids if Dad's not here in a few years? We've got a 10-month-old child. He's not even going to remember me. How are we going to talk to our 5-year-old?"
The tumor was likely to be benign, but it still required major surgery. Grand Rounds' data scientists evaluated not just individual doctors but also entire surgical teams for their experience and skill with a procedure that is performed only 3,000 times a year in the United States . Tripp ended up with a team at Stanford, but he talked to surgeons around the country, who told him he'd have to make a difficult choice: between preserving the ability to move his face and the ability to hear in that ear. For a CEO the choice was obvious: He couldn't imagine making deals with strange expressions on his face. He was under anesthesia for 11 hours as the tumor was scraped away from the nerve, layer by layer. When he woke up, he smiled broadly. His face wasn't paralyzed, but he was deaf in his right ear. "I think [the deafness is] a critical reminder of where I've been and why we're doing what we're doing," Tripp says.
In 2011 Tripp's cofounder , Stanford radiologist Rusty Hofmann, hatched the idea for Grand Rounds, originally called ConsultingMD, out of "pure frustration." Hofmann's office at Stanford was filled with FedEx packages containing medical records from desperate patients who were hoping he could help diagnose problems with blood clots in their veins, his area of expertise. He and his staff would go through the files at no charge. But there was little he could do, and the right records often weren't included. Could there be a business in triaging all such extra work that came into every academic physician's office?
Then the idea became deeply personal. In 2011 Hofmann's son, Grady, developed aplastic anemia, a deadly disease. Grady needed a bone marrow transplant. Normally, marrow comes from a sibling, but neither of the other Hofmann children was a match. Rusty was. Grady's doctors didn't know if using his father's cells would work, but Rusty called physicians at top-tier institutions and found some who had done transplants from parent to child--and they had worked. Grady got the transplant. Also, based on the advice of experts, Rusty cleaned the air-conditioning ducts in his house to cut down on germs in order to protect his son's weakened immune system. Visitors had to get flu shots. Grady, now 13, has braces, goes to school dances and surfs.
Grand Rounds co-founder Rusty Hofmann. Credit: Tim Pannell for Forbes.
The strain on his family was immense. What do people do when Dad isn't a doctor? "Every aspect of my life was feeling this pain," Hofmann says. "This has got to change. This cannot be the way we continue for the next 50 years in this country."
Hofmann had no clue how to turn his idea into a business. An early investor set up a meeting with Tripp at Tootsie's, a cafe near Stanford. Hofmann thought it was just a meeting to trade ideas. Tripp, who had previously cofounded Reputation.com, which helps people clean up their online records, had an inkling it might be more. The two hit it off instantly. Tripp was the son of a pediatrician and had intended to go into medicine before he got involved with starting one of the first wide-area Wi-Fi networks, in the early 2000s, at Trinity College in Connecticut, where he was a student. He'd gotten addicted to tech. Now he'd found a problem he thought technology could handle. Where Hofmann saw a service to help doctors filter patients, Tripp saw an opportunity for technological disruption.
"I saw this guy who is in the business of saving people," Tripp says. "That's why he does it, and that's what he's really good at. But he is not scalable. There was just no way that this guy was going to be able to meaningfully reach all the patients who would benefit."
Hofmann offered Tripp the CEO job that night on the phone, and they met for a follow-up dinner. Hofmann was convinced Tripp would turn him down. Instead, Tripp was so hyped about the meeting that he showed up despite the fact that he was shivering with a 102-degree fever, because he wanted Hofmann to know how excited he was. They didn't shake hands for fear of sending germs home to Grady, who was still sick.
Grand Rounds' first product would be to give second opinions, mostly to patients who had severe illnesses like cancer or who were considering big procedures like back surgery. The first 150 cases yielded a shocking surprise: Two-thirds of the time, Grand Rounds' experts would change the existing diagnosis or prescribe a new treatment. Often the original doctor got it wrong.
Medical errors are estimated to kill between 100,000 and 400,000 Americans annually. That makes it sound like people are dying because of dumb mistakes, but many errors are cases of misdiagnosis or mistreatment. A 2012 study estimated that a third of the U.S. health care budget--then $750 billion--is lost on wasteful care. Yet medicine has resisted one obvious solution: getting an extra set of qualified eyes on every case.
In fact, medicine has gone in the wrong direction. Thirty years ago it was common for insurance companies to require a second opinion before a major surgery. Grand Rounds takes its name from a long-standing medical ritual, in which complex cases are presented to an audience of doctors so that ideas can be exchanged and physicians can be sure they get the right answer. In other words, it's like doctors' rounds on steroids.
Of course, Grand Rounds' investors aren't in this game just to improve health care. They see a huge upside. Bryan Roberts, a well-known tech venture capitalist at Venrock, thinks Grand Rounds might someday play a role every time a patient picks a doctor. A couple of years ago he started offering Grand Rounds' services to Venrock entrepreneurs. "Within a couple months," he says, "I'd gotten three or four e-mails from our entrepreneur CEOs saying things like 'I think my dad's alive because you bought Grand Rounds for us.' "
Bob Kocher, another Venrock partner, who played a role at the Obama White House in crafting the Affordable Care Act, started a Grand Rounds case on his teenage niece, who had cancer. The second opinion confirmed her diagnosis but recommended freezing her eggs before her ovaries were damaged by chemotherapy. Her original doctors hadn't suggested that.
Grand Rounds employs a staff of 80 clinicians who interact with patients. The doctors' job is not to make diagnoses or correct mistakes but to deal with patients directly to help them understand what the experts said. Just handing a sheaf of papers to the patient without explaining it, Tripp says, is not enough to have an impact.
These staff physicians connect with patients, getting medical records and asking key questions, like how far the patient is willing to travel. Then they use Grand Rounds' database to match the patient with the right doctor. The company's database grades doctors on factors like where they trained, which other experts they trained with and how often they perform certain tests and procedures, based on insurance-claims data provided by Grand Rounds' customers. (Too many tests tends to indicate poor medical judgment.) The experts the company trusts are those who do best, according to a machine-learning algorithm, in literally hundreds of categories, including mortality data, readmission and complication rates.
Individuals can pay for Grand Rounds, but the company sees its big opportunity in selling its service to employers that want to reduce their health care costs. Like Costco (which, including part-timers, employs 218,000 people), many of Grand Rounds' customers self-insure. This means that while Aetna manages its health benefits, Costco is exposed to a certain amount of financial risk. The number of patients who use the service is small but increasing quickly, from about 90 patient cases a month when Costco started using Grand Rounds last January to 150 monthly cases now.
Patients are more likely to trust Grand Rounds than their own insurers. When an insurance company denies a claim, employees just become angry; they're willing to believe Grand Rounds if its doctors provide the same reason. "There's nothing like an objective party that is different from the insurance plan," says Donna Sexton, Costco's director of employee benefits.
Sometimes, of course, the original doctors got the diagnosis and treatment right, in which case Grand Rounds represents a powerful tool for getting the insurance company to pay. Leslie Nava, a personal trainer, got access to Grand Rounds through Costco, where her husband works part-time to get health benefits. She and her son both have a hereditary disease called neurofibromatosis type 2, which causes noncancerous tumors to grow throughout the nervous system. A tumor on her son's acoustic nerve was going to rob him of his hearing. The only thing that would preserve his hearing was regular treatment with the cancer drug Avastin. Aetna wouldn't pay.
"I probably sat there crying for ten minutes," Nava says. A nurse at the doctor's office told her that her insurance included Grand Rounds and that she might try the service. She did and was amazed by the personal care she got from the company's staff physician and relieved when the report came back saying that Avastin was, in fact, the best option. Aetna agreed to pay. "It definitely renewed my faith in the health care system," Nava says.
Privately held Grand Rounds won't discuss financials, but it seems to be growing fast. The service is now available to more than 3 million people through their employers. Tripp says that revenue has been increasing 100% a year for each of the past three years and that the company's customers include four of America's largest retailers and three major food manufacturing plants, as well as Autodesk and the Wahl Clipper Corporation. He's particularly proud that Grand Rounds is offering blue-collar workers the kind of medical care once available only to the rich.
"I think that's a frequent misconception that we are simply trying to help the 1% get 1% health care," Tripp says. "In fact, it couldn't be further from the truth. We're actually helping the 99% or the 90% get the 1% health care solution." If it works, it will be an amazing case of capitalism improving the world.
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e4f50d50509099c0804f9d0f0426a035 | https://www.forbes.com/sites/matthewherper/2017/01/06/declaring-war-on-germs-with-bill-gates-and-a-veteran-ceo/ | Leaving Biogen, CEO Scangos To Head New Firm That Battles Germs | Leaving Biogen, CEO Scangos To Head New Firm That Battles Germs
Most drug companies are retreating from the business of creating drugs against viruses and, especially, bacteria. But a well-funded startup being announced today is taking the challenge head-on.
The new company, called Vir Biotechnology, will be lead by George Scangos, who recently stepped down as the chief executive of Biogen, the Cambridge, Mass.-based biotech firm. It will be funded with a still-undetermined sum of hundreds of millions of dollars. The Bill & Melinda Gates Foundation, seeking new solutions for scourges like HIV and tuberculosis, will be among its biggest backers.
"Tremendous innovation is needed to control and potentially cure infectious diseases, including those that disproportionately affect the poorest people,” said Bill Gates, the world’s richest man, in a prepared statement. “Vir is a unique partnership that will allow us to leverage novel technologies to address these unmet needs together.”
Vir was founded by Robert Nelsen, a venture capitalist at ARCH Venture Partners. His firm will be committing $150 million to the new company, and Nelsen says that when it is completed the total fundraising would be the biggest ever–meaning it could be north of $500 million. (He spoke before another Nelsen-backed company, cancer test maker Grail, announced last night that it plans to raise $1 billion.)
Nelsen tends to play his passions, and says that this company was based on a simple one: he hates germs. More seriously, he noticed that drug companies were backing off infectious disease just as he thought the science of fighting them was getting new traction. Time for a deal. He recruited Vicki Sato, an immunologist who held top research posts at Biogen and Vertex Pharmaceuticals, to be the company’s chairman. Then, he approached Scangos, who decided this summer he would step down from Biogen because he was tiring of commuting from San Francisco. He hadn’t been planning to take a CEO job, but he says Vir completely captured his imagination.
“There's a huge need here,” Scangos says. “We're talking about hundreds of millions of people who are infected with some of these diseases. If you look at the chronic TB and other infectious diseases we're talking about hundreds of millions of people. There's a huge medical need. There is an incredible opportunity.”
At the core of the company is research being done by Louis J. Picker, a researcher at Oregon Health & Science University. Picker studies the way that T-cells, a component of the immune system, fight off infection. The idea, Sato says, is to try to replicate the kind of immune-system-boosting approaches that are showing success in cancer in fighting off microbes.
One of Picker’s projects is an HIV vaccine that uses cytomegalovirus, a relatively benign virus that stays with people for life. It has shown promise in primates. A similar approach is being explored in TB. This is initially what drew the Gates Foundation’s interest in making an investment in Vir. “It will be years before we get there,” cautions Emilio Emini, the director of the HIV program at the Gates Foundation. But Emini says the foundation was also excited about another prospect: that of spurring more industry interest in fighting germs. “It’s a new company with a focus on infectious disease and inherently that is very interesting and important.”
Vir’s leaders say they intend to invest in other platforms. More than that, they will use the hundreds of millions of dollars the company intends to raise to purchase experimental drugs being developed at big pharmaceutical companies. Some of these will have sales potential the drug giants think will be too small. Others will be getting de-prioritized as companies choose to focus on other areas. The advantage, Scangos says, is that it will be small and entrepreneurial like a biotech, but with a big pharmaceutical company’s ability to make many bets.
Twenty years ago, Scangos founded Exelixis, a biotechnology company focused on cancer. (He is still a director.) Last year, it was the third-best performing biotechnology stock, showing a 164% gain. But its stock looks like a roller-coaster over its history. During 2014, for instance, its share price fell 70%. “In a small biotech with limited resources, things can fail. If you're lucky, one of the early things succeed and you look like a genius,” Scangos says. “If the odds go against you, then you have the opposite issue.” Better, he says, to collect a small group of great scientists and write them a big check. Well, we’ll see. The world’s infectious agents will be hoping Scangos is wrong.
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3261872880ed84716479dd3adbb517f3 | https://www.forbes.com/sites/matthewherper/2017/01/09/illumina-adds-ibm-watson-to-dna-test-for-cancer-patients/ | Illumina Adds IBM Watson To DNA Test For Cancer Patients | Illumina Adds IBM Watson To DNA Test For Cancer Patients
(Photo by Ben Hider/Getty Images)
Illumina and IBM announced that they would be bundling IBM’s Watson Genomics product with Illumina’s TruSight Tumor 170, a tool used to help match very sick cancer patients with drugs that might help them.
The move is the latest effort by DNA sequencing companies to try to get doctors outside major cancer centers like Memorial Sloan-Kettering Cancer Center in New York or M.D. Anderson Cancer Center in Houston to try to scan patients' DNA. The idea is that the DNA test results can be used to help patients who don’t have any options find medicines–either approved or experimental–that might help them. So far, this is considered standard practice for late-stage non-small cell lung cancer, but not for cancers in general.
Illumina says the sale of DNA sequencing machines for use in cancer represents about 10% of its annual sales, or about $240 million. That includes the sale of DNA sequencers to medical centers and to companies such as Foundation Medicine and NantHealth, which sell analysis of the genetic tools to health systems or patients.
Probably 2 million Americans could benefit from having their tumor DNA sequenced, according to Steve Harvey, vice president of Watson Health. Yet fewer than 10%, and probably more like 5%, do. The goal of the new partnership is to make it simpler for a hospital to start doing DNA sequencing. “Illumina’s ability to bundle the Watson report along with the TruSeq 170 enables a cancer institute or a diagnostic lab to get up and running much quicker,” says Harvey.
For doctors and hospitals, there are two big questions: Which genes do they sequence, and how do they analyze the resulting data? Often, the solution is a so-called “tumor board” in which a committee of doctors analyzes the genetic data patient by patient.
The IBM-Illumina offering is simpler: the DNA sequencer is used only to analyze the 170 genes in the tumor that indicate that a medicine that is either approved or available in clinical trials now might prove effective. Within minutes, Watson Genomics can take that data and put out a report that tells what genes are mutated and what drugs might help patients.
IBM points its experience using Watson at the University of North Carolina’s Lineberger Comprehensive Cancer Center, which was highlighted on a recent episode of 60 Minutes, the news magazine show. Watson always found the mutations that the tumor board settled on, it says. But in 30% of cases Watson also found other mutated genes, which the tumor board agreed were important.
But there is another selling point for using Watson to find genetic chinks in a tumor’s armor, and it is economic, not medical. Services like Foundation Medicine or NantHealth offer far more–NantHealth promises to sequence the full tumor genome. All of these services, though, take the samples out of the hands of the person who has traditionally analyzed patient samples: the hospital pathologist.
What the new product offers a hospital pathologist is a way to buy an extra machine to run an extra test, without farming it out to a service outside the hospital. Illumina will sell the IBM analysis tool bundled with the reagents it sells with DNA sequencers. Even without knowing the cost, it’s easy to see how this would appeal to a pathologist: you’re not outsourcing an important test to somebody else. You’re doing it yourself, getting the credit and capturing the economics.
“They have access to the samples, and they are running the other molecular tests on the samples,” says Illumina chief executive Francis deSouza. “So for a lot of pathologists it makes sense to add this to a lot of the services they offer.”
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36d1af93a9b0a42cc334799678c034af | https://www.forbes.com/sites/matthewherper/2017/01/09/illumina-promises-to-sequence-human-genome-for-100-but-not-quite-yet/?sh=60fa3abf386d | Illumina Promises To Sequence Human Genome For $100 -- But Not Quite Yet | Illumina Promises To Sequence Human Genome For $100 -- But Not Quite Yet
Illumina, the largest maker of DNA sequencers, is launching a new DNA sequencer with new architecture it says could push the cost of decoding a human genome from $1,000 to $100–although that decrease will not come for years.
“This is good news, affirming that the field is still so healthy that price-plummeting is still considered good for business,” says George Church, the Robert Winthrop Professor of Genetics at Harvard Medical School.
The new DNA sequencers, called the NovaSeq 5000 and the NovaSeq 6000, could be about 70% faster than existing machines, by Church’s math–not a big increase in this field. But Illumina promises rapid increases as new parts and software upgrade the machines, meaning that by the end of the year the machines will be six times faster than its predecessors. Illumina has annual sales of $2.4 billion.
In 2006, Illumina’s first DNA sequencer could sequence a human genome at a cost of $300,000. For Illumina’s highest-end products, the cost is currently $1,000 per genome, including reagents and the amortization of its machines. The machines themselves are still costly: The NovaSeq 5000 and 6000 cost $850,000 and $985,000, respectively.
But those drops in cost have generated a huge amount of medical knowledge. Five years, ago, only a small number of human genomes had been sequenced. Two years ago, when Illumina made its last big product announcement, 65,000 human genomes had been sequenced. Now more than 500,000 have been sequenced, Illumina says.
"We feel like in the high end of the market this continues to put distance between us and any possible player in the market on any dimension: Quality, throughput or cost per genome,” says Francis deSouza, Illumina’s chief executive. “This is a phenomenal machine."
Illumina CEO Francis deSouza (Image courtesy Illumina)
However, deSouza said the $100 number was more a roadmap–something that would probably happen in more than three years and fewer than ten.
Prominent genomics researchers were happier about more prosaic features. First, new machines are individual machines–Illumina’s current top-line products, the X5 and X10, are sold in bundles and can’t be bought one at a time. Second, they don’t come with restrictions on what kind of research they can be used for. Illumina does not allow the X5 and X10 to be used for looking at what are called exomes: looking at only the parts of the genome that contain known genes. Those restrictions will still exist for the older machines, Illumina says.
“It's good they are moving away from the model of requiring users to buy a certain number of instruments as a bundle, and not allowing you to do some types of assays on an instrument you bought and paid for (dearly), which was just silly,” wrote Elaine Mardis, co-director of the Institute for Genomic Medicine at Nationwide Children’s Hospital in Ohio, in an email.
DeSouza says that the new machines are also easier to use, with the number of steps in its workflow cut from 38 to 8. The machine has been made more idiot-proof, with RFID chips checking to make sure components are loaded properly. Creating the new architecture, he says, required 17 major innovations across every part of the sequencer, although it uses the same basic chemistry as previous models.
Another question is read length. DNA sequencers actually only read small bits of DNA, which are assembled like a puzzle. The Illumina machine is still stuck at 150 base pairs (pairs of DNA letters). But some new technologies are allowing much longer readlengths–at a much higher cost per DNA base pair.
One is Oxford Nanopore, which already sells a portable DNA sequencer and is expected to launch one for laboratories this year. The question is whether Oxford can even make a dent in the Illumina marketing machine.
“I think there’s going to be blood in the water at some point in 2017 or 2018,” says Ewan Birney, joint director of the European Bioinformatics Institute. He notes that Nanopore, which he consults for, has some advantage. An experiment on its machine can be run in a matter of minutes or hours (one run on an the NovaSeq takes 40 hours) and that the Nanopore machine will only cost $75,000, which could help labs start to try it out.
Many other DNA sequencing upstarts–Ion Torrent, Pacific BioSciences, Complete Genomics--have tried and failed. None has even made a dent. At present, the company holds the vast majority of the market for DNA sequencing worldwide. But in order to make its investors happy, it’s also going to have to make that market grow beyond research. That's as big a challenge as any competitor.
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2d00416e2c1a094b48743ccfd2a2bfcd | https://www.forbes.com/sites/matthewherper/2017/01/19/epipen-competitor-auvi-q-to-be-free-for-most-patients-but-cost-4500-for-insurers-in-rube-goldberg-scheme/ | In Rube Goldberg Price Scheme, EpiPen Competitor Auvi-Q To Be Free For Patients, $4,500 For Their Insurers | In Rube Goldberg Price Scheme, EpiPen Competitor Auvi-Q To Be Free For Patients, $4,500 For Their Insurers
Auvi-Q, the main competitor to EpiPen, is announcing a convoluted pricing strategy try to make sure patients will be able to get access to its injection for treating life-threatening allergic reactions.
Kaleo, Auvi-Q’s manufacturer, will charge patients who have commercial insurance $0 for the product, whether or not the insurance company pays for it. It will also give the product away to families with an income of less than $100,000. For those paying cash who do not qualify to get Auvi-Q for free, the product will cost $360.
But the list price for Auvi-Q, and the starting point for insurance companies, will be much higher: $4,500, 7.5 times the list price drugmaker Mylan charges for EpiPen. Last year, Mylan faced a firestorm of scrutiny, including Congressional hearings, for raising EpiPen’s price 600% over a period of years. Mylan’s chief executive, Heather Bresch, has blamed the price increase in part on the same baroque system that Kaleo is trying to navigate.
Also on Forbes:
Checking whether patients have insurance, and getting reimbursement, would be handled by a network of specialty pharmacies that will work with Kaleo. Kaleo will pay insurers directly any cost-sharing or co-payments insurers charge patients. That means that for insured patients, Auvi-Q would be the cheapest option—even cheaper than the no-frills generic injector CVS will sell for $100 through a collaboration with the drug firm Impax.
“The most important thing to us is patient access and affordability,” says Spencer Williamson, Kaleo’s chief executive. “Our company was founded by patients, and we put patients first.”
Eric and Evan Edwards, the twin brothers who invented the Auvi-Q device.
Auvi-Q was invented by Evan and Eric Edwards, twin brothers who, as children, suffered from severe allergies to eggs, shellfish and nuts. Evan became an engineer, and Eric a doctor, and together they decided to create a device that would be better than existing epinephrine auto-injectors like EpiPen. The device is smaller than EpiPen—about the width and length of a credit card—and gives verbal directions of how to use it, something that can help a panicked parent or bystander when a victim, perhaps a child, goes into anaphylactic shock.
The product was first launched in partnership with Sanofi in 2013. Sanofi charged about the same price as for EpiPen, but Auvi-Q was prescribed only 10% as often as its competitor. The Auvi-Q was withdrawn due to manufacturing problems Kaleo says it has fixed. Williamson says that the old pricing strategy did not get Auvi-Q into the hands of patients who needed it, and led to the new approach, which he describes as “bold.” But experts were skeptical of Auvi-Q’s strategy.
“It’s a very weak position. If I’m the payer I’m just going to block the product, I’m not going to pay for it,” says Richard Evans, an analyst who follows the pharmaceutical industry for Sector and Sovereign, a consulting firm. “If you’re going to give it away, fine, knock yourself out. What is my motive to pay $4,500, or any derivative of $4,500?”
Adam Fein, president of Pembroke Consulting and author of the blog drugchannels.net, was even more skeptical, comparing the approach to that of Valeant Pharmaceuticals, which fell into disrepute because of the way it used specialty pharmacies.
“Frankly it sounds a lot like a Valeant strategy, where you set a very high list price and you only capture the reimbursement on a very small percentage of prescriptions,” Fein said. “Instead of getting a reasonable price for everything, you are going to get nothing from most of the market and a lot from a very small percentage of the market. It’s almost an outdated strategy that seems designed to invite controversy.”
Williamson bristles at those criticisms. “We are very encouraged by the number of plans that we believe are going to cover Auvi-Q,” he says. Health plans, he says, want to support innovation and to show their members they are protected. He says there is “no comparison” between Kaleo, which he says is just putting patients first, and Valeant.
“We have seen what happened to Auvi-Q when it was on the market before,” Williamson says. “We saw Auvi-Q priced nearly identical to the other brand on the market. Patients had real access problems. I can’t tell you how many physicians have told me how difficult it was to get Auvi-Q to their patients.”
In one case, Williamson says, the insurance company demanded a patient be blind to get the product. “That’s just crazy,” he says. “We’ve got stakeholders in this system that we believe put economics in front of patients. And at Kaleo we’re always going to put patients first."
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fece87cae09228e7887fb397022bba8f | https://www.forbes.com/sites/matthewherper/2017/02/10/a-6000-price-hike-should-give-drug-companies-a-disgusting-sense-of-deja-vu/?sh=317c910971f5 | Why Did That Drug Price Increase 6,000%? It's The Law | Why Did That Drug Price Increase 6,000%? It's The Law
Groundhog Day, anyone? (Photo by Andrew Burton/Getty Images)
It’s happened again. Of course it has happened again. A drug company has brought a drug that has been available as a generic elsewhere in the world for decades at a shockingly inflated price.
The drug, in this case, is a steroid called deflazacort, has been approved for treating kids with Duchenne muscular dystrophy. It has fewer side effects than existing steroids, and many patients have been getting it from Europe or Canada at a price between $1,000 or $2,000 a year.
Yet a pharmaceutical company in Deerfield, Ill., has gotten approval from the U.S. Food and Drug Administration to sell deflazacort (snazzy brand name: Emflaza). The company, Marathon Pharmaceuticals, is charging a list price of $89,000 – a 6,000% price increase.
If this doesn’t feel like déjà vu all over again, you haven’t been paying attention. Yes, it was a 5,000% price increase on a drug for a rare infection that made Martin Shkreli, then chief executive of Turing Pharmaceuticals, “the most hated man on the Internet.” But Shkreli’s was an incremental innovation in price gouging. Before that, we had the case of Makena, used to prevent pre-term birth. It was launched in 2011 at a price of $1,500 when a similar drug was previously available, from compounding pharmacies, for $20. The strategy basically worked: AMAG Pharmaceuticals, which now owns Makena, booked sales of $93 million in the third quarter of last year.
Why does this keep happening? Well, with the exception of Shkreli, enabled by a thicket of market inefficiencies, because it’s the law. And that’s very much the case for Marathon and Emflaza.
Because this steroid has never been approved in the United States, the Food and Drug Administration considers it a new drug. That means that not only did Marathon have to go through the process of getting it approved as a new drug, but that it gets the benefit of laws Congress has passed to encourage drug companies to develop new medicines for rare diseases.
Those legal benefits include a 7-year monopoly under the Orphan Drug Act, and a rare disease priority review voucher that allows a company to get a sped-up FDA review for another drug. Such vouchers can be sold for large sums.
The idea behind those benefits is that society needs to pay in order for drugs for rare diseases to be developed. It seems obvious that getting a generic steroid that is approved in the rest of the world through the FDA should not have the same benefits to a company as inventing a new medicine. Yet, under the law, it does.
This isn't Shkreli-level malfeasance. Mitigating factors: Marathon says that only 7% to 9% of the patients who could benefit from Emflaza were able get access to it by importing the drug from other countries. In order to get the FDA approval, Marathon conducted 17 clinical and pre-clinical trials, and had to go back and find the data from studies conducted by the drug’s original manufacturer. The FDA is making Marathon conduct post-approval studies, including one in children younger than five.
Does this justify a 6,000% price increase? Marathon says it actually expects to net “only” $54,000 a year from insurers. The company has also said its business will not be profitable for several years. It expects patients with insurance to get access to the drug for a co-payment, and will give it away to others for free. In other words, the high cost of this medicine is not intended to gouge patients, but to get us all to pay not only for the cost of getting the drug through FDA, but also to provide a big profit that will incentivize drug makers to bring more drugs to the United States.
This lays bare one of the absurdities of the FDA process: for a drug to be approved, a company must do the work of bringing it to market. For new medicines, developed at high cost by pharmaceutical companies, this is the right approach. But for medicines that have been in clinical use for decades it may not be. Imagine how much money we would all save if we paid for the National Institutes of Health to survey such drugs, collect real-world data on them, and have the FDA approve them without giving any company exclusivity? Then generic drug companies would make the medicines at much lower cost. Senator Ted Cruz has argued that drugs approved by European or Canadian regulators should automatically be approved in the U.S. That’s not a good idea, because it would lead to manufacturers of new medicines always going to whoever set the lowest bar. But for old medicines a system like that may make sense.
That’s not the system we have. Marathon is increasing the access of boys with a deadly disease to a medicine that will help them, and charging what it thinks is an honest price based on the regulatory burdens it has. That doesn’t make the price OK. But it’s how executives can convince themselves that what they are doing is OK.
The problem is, it’s not OK. The price is absurd, and the price increase short-circuits the fairness circuitry built into the human brain. There’s some amount that Marathon should charge for the work it did. But is it $85,000 per patient, or even $52,000? Probably not. And that priority review voucher itself could be worth hundreds of millions of dollars. Congress is obsessed with these vouchers. Maybe they're not the best solution to problems in the pharma business?
Marathon is a member of the Pharmaceutical Research and Manufacturers of America (PhRMA), the drug industry trade group. Drug companies cannot use their usual argument of saying this is an “outlier.” This is one of their own – although Marathon may find itself feeling as if it is being ostracized from the club. As patent lawyer Rachel Sachs notes, the big drug giants need to distance themselves from this move – and maybe find a way to actually come to the table on preventing big drug price increases.
Pharmaceutical company executives, here is your problem: You won’t get credit for the wonderful innovations your companies produce if your prices make people feel sick.
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aab4ca6dc582ee2291815085df213eb4 | https://www.forbes.com/sites/matthewherper/2017/03/07/15-million-people-could-lose-health-insurance-under-the-gops-obamacare-replacement/ | 15 Million Fewer People Might Have Health Insurance Under The GOP's Obamacare Replacement | 15 Million Fewer People Might Have Health Insurance Under The GOP's Obamacare Replacement
Donald Trump waves after speaking as Vice President Mike Pence and U.S. House Speaker Paul Ryan... [+] applaud during a joint session of Congress in Washington, D.C., on Feb. 28, 2017. Photographer: Andrew Harrer/Bloomberg
Last night House Republicans released a draft bill that would repeal the Affordable Care Act–the law known as Obamacare. “Time to end this nightmare,” President Donald Trump tweeted. But the new bill is likely to draw fire from both the right and the left, and turning it into a law could become a slow, drawn-out process.
“This bill is going to cost more than they expect and not cover as many people as they think,” says Bob Kocher, a venture capitalist at Venrock who served in the Obama Administration as one of the ACA’s architects. “I think this could collapse under its own weight.”
The basic outline of the plan: It would eliminate the individual mandate, which requires that all people buy insurance, and the subsidies designed to make that insurance affordable for low-income people. It replaces those subsidies with a refundable tax credit based on age, not income, that includes an income test. It would change the way that Medicaid, the government program to provide insurance to poor people, functions. Under the new law, the federal government would give block grants to states instead of paying them based on their actual costs. Many of the ACA’s protective regulations would be removed.
Opponents of the ACA argue that it is in dire need of replacement: In some states, premiums have soared as insurers have been unable to lure enough healthy people to buy plans. Big insurers, including Aetna and UnitedHealthcare , have exited some or all of the exchanges the ACA created. But repealing, replacing or repairing the ACA has a big hurdle: political plausibility.
Will 15 Million Fewer People Be Covered?
House Republicans have decided not to wait for estimates from the Congressional Budget Office on how much the bill will cost and how many people it will cover before they start to revise it. But those figures will matter.
Matthew Fiedler, a fellow at the Brookings Institution, a left-leaning think tank, estimates that at least 15 million fewer people would have health insurance under this plan than if the Affordable Care Act were left in place. He thinks this estimate is low, and that the CBO could come out with a higher number. Avik Roy, Forbes’ opinion editor, puts the number even higher, at 20 million, in his must-read assessment of the bill. By comparison, the Robert Wood Johnson Foundation estimates that eliminating the ACA entirely would result in 24 million fewer Americans with health insurance.
Here’s what goes into Fiedler’s figure: About half of the ACA’s coverage gains come from Medicaid, the other half from the exchanges where people who don’t get health insurance through their employers can buy it. Fiedler thinks repealing the individual mandate results in a loss of 15 million lives covered. Increased funds for reinsurance and penalties for enrolling late could decrease that figure. But the undoing the match given to states on Medicaid will result in some people being taken off the rolls. It probably nets out, he says, at 15 million or more.
What Will The Senate Do?
One question is whether this bill, in its final form, will be able to pass the House of Representatives. But the House passes a lot of bills. The bottleneck for getting the bill through is likely to be the Senate, where Republicans have only a thin majority.
Four Republican senators have already voiced opposition to the bill because of the changes to Medicaid. All of them--Shelley Moore Capito of West Virginia, Cory Gardner of Colorado, Rob Portman of Ohio and Lisa Murkowski of Alaska–hail from states that signed up for Obamacare’s Medicaid expansion. In order to pass a bill, even by the budget reconciliation process that applies only to financial legislation, at least two of those four would need to sign on.
“We view this legislation as a starting point that is likely to eventually move closer to ACA coverage levels to have a chance of passing–and thus we do not expect a significant market reaction on Tuesday,” wrote Michael Newshel, an analyst at the investment bank ISI Evercore who covers managed care organizations and hospitals.
Some of the changes made by the bill–like health plans for seniors to be six times more expensive than those for younger people, instead of three times–might not be passable through the reconciliation process, meaning Republicans would need to convince Democrats as well.
What Happens To Current Health Plans?
Adding to the drama, Republicans face real deadlines in getting a plan put in place. Next month, health insurers will start making decisions about whether to offer plans on the ACA exchanges. Increased uncertainty about whether those exchanges will even exist could lead more plans to exit the ACA exchanges because they are losing money. The uncertainty created by the legislative progress could make the Obamacare health insurance more expensive.
Another big question for the CBO: will the GOP plan affect people in employer-based plans? On March 6, conservative policy consultant Christopher Jacob, who previously worked for House Republicans, published an analysis of the forthcoming bill that argued that the GOP’s plan could result in many employers dumping their employees into the individual market. The reason: the GOP plan’s decision to use age-based tax credits means that employers with young, healthy employees might simply decide to drop them. The new bill limits who gets the credits based on income. Will that be enough to offset that risk?
A big factor to watch: at what point does the White House put its weight behind a plan? With the Affordable Care Act, the initial act passed by the House was only a rough draft of the final law that was crammed through the Senate. It seems the wrangling has just begun.
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41944dcac44c751d40112a5709313ef3 | https://www.forbes.com/sites/matthewherper/2017/04/03/for-bristol-myers-cancer-drug-a-victory-and-a-mystery/ | For Bristol-Myers, A Victory And A Mystery | For Bristol-Myers, A Victory And A Mystery
New data presented at a medical conference show that combining Bristol-Myers Squibb’s two immune-boosting cancer drug appears to extend the lives of melanoma patients longer than using either alone.
But a big question lingers about one of the drugs, Opdivo: why did it fail to extend survival in patients with previously untreated non-small cell lung cancer, when a very similar drug from Merck proved effective? A trial being presentd this afternoon may yield some clues. Both studies are being presented at the annual meeting of the American Association for Cancer Research.
“I think that’s obviously been the topic of debate for the last seven or eight months,” says Naiyer Rizvi, director of thoracic oncology at New York-Presbyterian/Columbia University Medical Center, of the lung cancer failure. “I don’t thnk anyone has an answer.”
Billions of dollars are at stake. Last year, Bristol sold $3.6 billion worth of Opdivo globally, compared to $1.4 billion of Merck’s Keytruda. But because of the discordant lung cancer results, financial analysts at J.P. Morgan forecast that next year, the Merck drug will take the lead, with $6 billion in annual sales, compared to $4.8 billion in sales for Opdivo. Bristol shares are down 18% over the past 12 months as a result of the lung cancer result, while Merck shares are up 17%.
The melanoma results will be welcome news against that backdrop. The 945-patient study compared Opdivo alone, an older Bristol melanoma drug called Yervoy, and the combination of the two. Researchers already revealed that the Opdivo slowed tumor growth more than Yervoy, and that the combination slowed tumors more than either alone.
But skeptics worried that wouldn’t translate into longer lives for patients, particularly since once patients’ tumors grew, they were allowed to switch to the Opdivo-Yervoy combination. Extending patients’ lives in the control group could make the trial look less positive. The concern was heightened because the combination was approved by the Food and Drug Administration on an accelerated basis, which means the approval could have been withdrawn if the results disappointed.
The worries were unfounded. The median survival for patients on Yervoy was 28 months; a median had not been reached for Opdivo alone or the combo. At two years, 64% of those on the Opdivo-Yervoy combo were alive, compared to 59% of those on Opdivo alone and 45% of those on Yervoy. Both the combination and Opdivo were significantly better than Yervoy alone. The difference between Opdivo alone and the combination was not statistically significant.
The data are being presented here in Washington, D.C., at the annual meeting of the American Association for Cancer Research.
Fouad Namouni, who heads studies of the drugs at Bristol, called the result “a major advance.”
Serious side effects were more common with the drug combo than with either drug alone. Financial cost is also an issue: the combination has a list price of a quarter of a million dollars.
Given the positive results in skin cancer, and also in lung cancers that have not been helped by other treatments, why didn’t Bristol succeed in previously untreated lung cancer patients, the biggest market for these immune-boosting cancer drugs?
Researchers have been scratching their heads asking that question. Most are fairly certain that the answer is not that Opdivo is that different from Merck’s Keytruda. More likely, it has to do with differences in how the studies were designed. One difference, Rizvi posits, could be in the diagnostic tests that Bristol and Merck used to determine if patients’ tumors had high levels of a protein, called PD-L1, that predicts a better response to these drugs.
Another possibility is that the group that got Opdivo wasn’t as similar to the control group that received chemotherapy as it should have been. Another predictor of whether Opdivo and Keytruda are effective may be how many mutations have built up in the cancers they are attacking, a measure called tumor burden. Only 29.7% patients had a high tumor burden in the Opdivo arm of the failed study, compared to 39% in the chemotherapy arm, according to an abstract released at the meeting. Full results are scheduled to be presented at 5:20 pm ET this evening, and Wall Street analysts, researchers, and drug company execs will all be watching for clues of what exactly went wrong in Bristol’s trial.
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6360a3e2358db1dba9f3cefb5ec638e0 | https://www.forbes.com/sites/matthewherper/2017/07/05/to-gag-a-shkreli/ | To Gag A Shkreli | To Gag A Shkreli
It’s all the journalists’ fault that Martin Shkreli is talking, his lawyer insisted this morning. The lawyer, Benjamin Brafman, told a judge that “certain representatives of the press” have gone out of their way to “bait” Shkreli into making public statements.
This seems like a strange claim, given that last week Shkreli, infamous for raising the price of a generic drug and on trial for allegedly defrauding investors in the hedge fund he ran, actually barged into the separate room at the federal courthouse in Brooklyn where reporters were working last week. It seems stranger given Shkreli’s willingness to talk.
Take an interaction I had with him last week, as proceedings ended in the courthouse's marble lobby. It was regarding a Twitter account, “@BLMBro,” that seemed to belong to Shkreli, who had previously been banned from the social media platform for harassing a female reporter. I asked him if the account belonged to him.
Martin Shkreli, former chief executive officer of Turing Pharmaceuticals AG, arrives at federal... [+] court with his attorney Benjamin Brafman in Brooklyn on July 5, 2017. Photographer: Peter Foley/Bloomberg
“Are you ratting me out to the AUSA?” he asked, referring to the federal attorney. I misheard him as asking if I would rat him out to USA Today. I said I was the same guy who wrote for Forbes he’d spoken to before. He laughed, and repeated himself. I said I was looking for a comment for publication. He said he was “not going to confirm or deny” that it was his account. “Black lives do matter, though,” he said, referencing the account name.
On Monday, the prosecutors filed a motion to prevent Shkreli from communicating with the public based on comments he'd made to the press during the trial and, allegedly, via the BLMBro account. Judge Kiyo Matsumoto seemed most concerned that Shkreli had made his comments in places that were in or near the courthouse, when jurors might hear them, leading to a mistrial. Twitter, apparently learning from the reports on the District Attorney’s filings that BLMBro is Shkreli, shut down the account. My point is: he talked freely, eagerly and calmly.
Shkreli’s activity on social media seems likely to continue. He’s only “gagged” in the vicinity of the courthouse. The rest of the world can continue to consume all the drama he generates on Facebook chats. He seems anything but afraid that the publicity will hurt his case, or lead to a mistrial. One thing about Martin Shkreli: he’s not good at keeping his mouth shut. That’s partly how he became infamous in the first place.
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a0c1e601fd6effa02890ee887faa4cb6 | https://www.forbes.com/sites/matthewherper/2017/08/09/biotech-wunderkind-raises-1-1-billion-to-fund-pharma-startups/ | Biotech Wunderkind Raises $1.1 Billion To Fund Pharma Startups | Biotech Wunderkind Raises $1.1 Billion To Fund Pharma Startups
Vivek Ramaswamy, a former hedge fund partner who went on to engineer one of the biggest biotech initial public offerings in history, has a new source of cash: his investment vehicle, Roivant Sciences, just raised $1.1 billion from investors including the Softbank Vision Fund and Dexcel Pharma.
Vivek Ramaswamy Forbes
Ramaswamy's unique model is to raise large amounts of money for Roivant, which had previously disclosed a $700 million fundraising, and to use that fund to start still more companies, which in turn do their own fundraisings, either on the public markets or through a second set of private investors. Roivant has invested in a series of spinouts, including Arbutus (viral diseases), Axovant (neurology), Myovant (women’s health and endocrine diseases), Dermavant (dermatology), Enzyvant (rare diseases), and Urovant (urology). The new funding will go toward creating another 'vant, called DataVant, focused on accumulating siloed data to help judge the odds of success for drugs in clinical trials. Ramaswamy was a member of the Forbes 30 Under 30, and was on the cover of Forbes in 2015.
"The ball's in our court, but I hope we’re going to be doubling down or tripling down on the business model in the coming months if not the coming years," Ramaswamy says.
And Ramaswamy, who turned 32 today, has been able to lure some of biotech's biggest management talent to run these entities. David Hung, who took sold Medivation to Pfizer for $14 billion, recently took the helm at Axovant. Hung's second-in-command at Medivation, Lynn Seely, took the helm at Myovant. Jacqualyn Fouse, the former chief financial officer at Celgene, was recently appointed the executive chairman at Dermavant.
Ramaswamy's big idea is approaching it's first public test. Next month, investors expect data from a pivotal trial of Axovant's Alzheimer's drug, intepirdine. High hopes for the drug, initially discarded by GlaxoSmithKline, led Axovant to raise $360 million in its 2015 IPO. But it's been more than a decade since an Alzheimer's drug reached the market. The failure of similar drugs from Pfizer and Lundbeck has stoked widespread investor skepticism, which has been tempered mainly by Hung's willingness to take the helm. If intepirdine relieves Alzheimer's symptoms and improves memory, as Ramaswamy expects, it could be a multi-billion-dollar product. If it fails, it could make it harder for him to raise more cash until he notches a success -- although, with a war chest this big, maybe he won't need to.
“It’s Alzheimer’s disease," Ramaswamy says. "We’re swimming against industry odds. My feelings haven’t changed since we started the study. As much for our sake as for a field that needs it, I hope it works.”
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e5a3ad27b8c479aeb04efe63710c3e5c | https://www.forbes.com/sites/matthewherper/2017/10/16/the-cost-of-developing-drugs-is-insane-a-paper-that-argued-otherwise-was-insanely-bad/ | The Cost Of Developing Drugs Is Insane. That Paper That Says Otherwise Is Insanely Bad | The Cost Of Developing Drugs Is Insane. That Paper That Says Otherwise Is Insanely Bad
A group of white elephants trumpet. ( ROBERTO SCHMIDT/AFP/Getty Images)
It was six men of Indostan, to learning much inclined, who went to see the elephant (Though all of them were blind), that each by observation, might satisfy his mind." --"The Blind Men and the Elephant," John Godfrey Saxe
You probably know this poem, or at least the story it tells. One man likens the elephant to a wall, another to a spear, a third to a snake, a fourth to a tree. The point is that each sees only part of the animal, and is thereby deceived. Well, here’s how the same thing happened when it came to a new estimate of the cost of developing a new medicine.
For years, the pharmaceutical industry has relied on estimates from the Tufts Center for the Study of Drug Development, the most recent of which that puts the cost of bringing a medicine from invention to pharmacy shelves at $2.7 billion. Last month, two cancer researchers grabbed headlines by asserting that estimate is way off. Their number, published in JAMA Internal Medicine: $648 million. In an editorial that ran alongside the new study, journalist Merrill Goozner wrote: “Policymakers can safely take steps to rein in drug prices without fear of jeopardizing innovation.” There are reasons to think that (more on that later), but this paper does not add to them.
Unfortunately for the authors, pharmaceutical investors, and people fighting to control drug prices, the $648 million estimate doesn’t stand up scrutiny. A closer look at the authors’ own data raises problems with their analysis. A larger data set I published four years ago, when taking into account the study’s implicit arguments, yields a figure of about $2 billion. This study doesn’t upset the previous work on drug development costs at all. In fact, the data present a highly consistent picture – if you know whether you’re holding a tusk, a trunk, or a tail.
A primer: The amount spent to develop any individual drug depends mostly on what it costs to conduct studies to prove it is safe and effective and secure regulatory approval. That can range from $10 million to $2 billion, depending on what the drug is for. But what really drives up costs is the fact that 90% of medicines that start being tested in people don’t reach the market because they are unsafe or ineffective. The $2.7 billion figure includes the cost not only of these failures, but also of not putting the money spent on them into something that would give a more reliable return.
The authors of the new study, oncologists Vinay Prasad from Oregon Health & Science University and Sham Mailankody from Memorial Sloan Kettering Cancer Center, think that large companies inflate these costs through inefficiency or worse. So they chose to look at the 10 companies that developed only a single cancer drug from 2006 through 2015. The $648 million figure is simply the median R&D spending of these 10 companies.
The number of drugs under development by 10 biotech firms evaluated by Prasad and Mailankody, versus... [+] their R&D spending. Jama Internal Medicine
Prasad and Mailankody assert this analysis takes into account the high attrition rates of drug development because each company was developing between 2 and 11 experimental medicines, only one of which reached the market. But this assumes that the companies were developing a large enough number of medicines to capture the high failure rate of drug development. Given that 9 in 10 medicines fail, it seems unlikely that looking at companies that had made 4.3 attempts at creating a drug, on average, would capture this. Conceptually, this is no different from simply looking at companies that had only tried to develop a single drug and happened to succeed. Researchers call this “survivorship bias” – it’s like estimating an average lifespan by asking people their ages, but not finding out if anyone already died.Just graphing the amount spent by each company in Prasad and Mailankody’s data set makes it plain that they didn’t overcome survivorship bias. Generally speaking, the more drugs a company was developing, the more it spent on R&D per drug. How can you tell how many times you have to try to develop a drug to have good odds of doing so from this? You can’t.
I previously tried to address this problem with a data set 10 times bigger than Prasad and Mailankody’s. In 2013, working with Bernard Munos of the consultancy Innothink, I did an analysis of 100 drugs, looking at the R&D costs their makers had spent over the preceding decade in order to try to determine the average cost per drug. (You can see the whole data set here.) Here’s what happens if you plot the number of drugs approved (not just under study) against the total amount of R&D spending from that data set.
The number of drugs developed and 10-year R&D spend for 100 different companies. Herper and Munos, 2013
Notice that no company with R&D spending of less than $3 billion a year developed more than six drugs over a 10-year period. The median per-drug R&D spending of companies that developed more than six drugs – that’s only 8 companies – was $5.8 billion.
One reason for that high cost is almost certainly the high failure rate. Another is that big companies have other costs they include in the R&D line. These include studies done after a drug is approved. Some of these studies exist for marketing, but they also include the studies that proved, for instance, that statin cholesterol drugs extend heart patients’ lives. But other big costs, like safety reporting, are also included, and certainly inflate this figure. Those costs are not included in the Tufts estimate.
Meanwhile, the 66 companies that had only one drug approve spent between $15 million and $13 billion (Abbott Laboratories was having a bad decade). Median cost: $353 million, half Prasad and Mailankody’s estimate. Average cost: $953 million. It’s hard to look at that data set and not worry that Prasad and Mailankody are just basing their analysis on the lower left corner of the above graph. But from this data set, companies that develop multiple drugs and spend only $648 million aren’t average. They’re incredible outperformers, as you can see from the graph of the cost-per-R&D spending and the number of drugs approved for all 100 companies below.
The amount spent per drug, versus the number of drugs developed. Herper and Munos, 2013
Prasad and Mailankody really are not presenting data that upset the understanding of drug development. They’re pushing an opinion: they believe looking at large companies to leads to an inflated estimate of the cost of drug development. They have a point. As I pointed out in 2013, companies that spent more than $20 billion in R&D over 10 years spent $6.3 billion per new drug, compared to $2.8 billion for those that had budgets of between $5 billion and $10 billion. Brobdingnagian firms spend more.
So, taking Prasad and Mailankody’s implicit criticism to heart, I went back and looked at companies that spent less than $30 billion over a 10-year period. Those that had managed to get more than two drugs to market had a median R&D spend of $2 billion per drug. Those that brought four or more drugs to market had a median R&D spend per drug of $2.4 billion. That converges on the Tufts figure.
The real problem is that the amount spent to develop every new drug seems to be increasing. Prasad and Mailankody present the $2.7 billion Tufts estimate as being in contrast with an estimate of $320 million produced by the group Public Citizen. But the Public Citizen estimate, which is also based on R&D budgets divided by the number of drugs approved, is based on drugs approved in the 1990s. And the most obvious explanation for the difference is that the R&D dollars spent per drug have increased ten-fold in two decades. This is exactly the observation that Jack Scannell and his co-authors noted in Nature Reviews Drug Discovery in 2012, calling it “Eroom’s Law” – the reverse of the tech industry’s Moore’s Law, which predicts that transistors become exponentially cheaper over time.
Quibble about the details, but pharma companies do really spend billions for every drug that reaches the market. So, then, the elephant in the room: Do high R&D costs justify high drug prices? Of course not. Not by themselves. The medicines have to be worth the money, too.
You’ll pay more for a Tesla than a Ford Pinto not because of the money Tesla spent on research and development but because the result is a cooler car that runs on electricity, not gasoline. But if a car salesman told you he’d spent $2 billion on R&D, then presented you with a Pinto, you wouldn't pay. You'd walk out. Drugs are different – they save lives – but the same principle should apply. The idea that consumers should cover all R&D costs, no matter how wasteful, is obviously absurd.
Pharmaceutical companies like to imply that the U.S. market should cover all the money spent on R&D. But this isn't true.In order to get people to play Lotto, the government does not need to pay winners all the revenue collected from tickets. That's why money from state lotteries can be used to fund other things, like education. One of the most valuable conclusions from Prasad and Mailankody is the drugs they studied had median sales of $1.7 billion, and average sales of $7 billion. For these companies, investing in R&D paid off. One advantage of biotech startups is that they need not carry the costs of accumulated failures like larger pharmaceutical firms. If they fail, they can simply dissolve.
Cancer drugs are expensive enough to justify Pharma’s R&D. We know this, because more medicines are in development for cancer than any other disease. And the launch price of a new cancer drug has doubled over the past 20 years. It obviously doesn’t need to double again. A sane drug pricing system would start refusing to pay full price for more marginal cancer drugs, and would offer more for drugs that are not being developed, like antibiotics, because drug-resistant bacteria pose a gigantic threat to modern society.
The industry gravitates toward areas with lower risk, lower costs, or higher prices. That's the reason for not only the popularity of the market for rare diseases. In my data set, rare disease firms Biomarin and Genzyme (now part of Sanofi) had per-drug R&D costs of $195 million and $963 million, far below the average cost. We're deciding which drugs we get with these incentives. Of course lawmakers and bureaucrats should feel empowered to be thoughtful and conscious about these decisions. Drugs can be, and often are, too expensive. It is also true that if drug prices drop too low, no company will want to develop drugs. There needs to be a balance, and right now the market we built is not creating it.
But believing drug prices are too high does not justify coming up with a flimsy figure to counter the drug industry’s arguments about its R&D expense. In fact, recognizing that R&D is extremely expensive is a fundamental fact that explains why drug companies behave as they do. Besides, the best way to make sure pharmaceutical firms serve patients is to fight for high-quality data. The Prasad and Mailankody paper did the opposite.
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b7987c9768f1e21f47e91dd038ab2a8f | https://www.forbes.com/sites/matthewherper/2017/11/09/new-drug-eases-postpartum-depression-in-victory-for-tiny-sage-therapeutics/ | New Drug Eases Postpartum Depression In Victory For Tiny Sage Therapeutics | New Drug Eases Postpartum Depression In Victory For Tiny Sage Therapeutics
An experimental drug improved symptoms of post-partum depression within a matter of days in a hard-won victory for antidepressant drug development.
It is, of course, also a big win for Sage Therapeutics, the Cambridge, Mass.-based biotechnology company that is developing the medicine, even though the benefit was smaller than earlier, preliminary results. Sage will file for approval with the Food and Drug Administration in the first half of next year. The company’s shares are up 40% to $87.86 in morning trading. The data were made public in a press release, and have not yet been published in a medical journal.
Sage Therapeutics CEO Jeff Jonas Sage Therapeutics
Jeffrey Lieberman, the chair of psychiatry at New York-Presbyterian Hospital, called the result “Very interesting and encouraging.” He said: “It’s the first window into a novel mechanism for antidepressants.” Lieberman was not involved in the conduct of Sage’s trials.
The drug, brexanolone, helped patients by a statistically significant margin in two studies. In the first, women with severe post-partum depression improved between three and six points more on the 29-point Hamilton depression (HAM-D) scale compared to those taking a placebo, depending on dose. In a second study in moderate depression, women improved two points more than those who received placebo.
Brexanolone is given as an infusion that takes sixty-hours, or two-and-a-half days, which could be an impediment to using it for patients who are not so ill they need to be hospitalized. But the medicine has an advantage over existing anti-depressants, which can take weeks to become effective. It appears to work within 48 hours, and Sage says the effect seems to persist at least 30 days after treatment.
Sage was bedeviled by a problem that has driven the development of new treatments for depression to a standstill: the fact that patients get better on placebo in clinical trials. In an earlier study of 10 patients, women had a reduction of 22 points on HAM-D, 12 more than placebo. In the 122 patient severe depression study, those who received a high dose (90 micrograms per kilogram per hour) improved 17.7 points, three more than those on placebo. Those on a lower dose (60 μg/kg/hr) improved 19.9 points, 5.9 better than placebo. In the moderate study 104 patient moderate depression study, women receiving brexanolone improved 14.2 points, compared to 12 on placebo.
The extremely positive result of the first study was probably due in part to chance. But the increasing placebo effect is very much what is seen in other studies of antidepressants. “Placebo effects are directly related to severity,” Lieberman says. “In the more severe, you’ll have lower placebo effects. In the less severe you’ll have higher placebo effects.” Existing antidepressants tend to have a HAM-D benefit of about four points. In the moderate patients, the improvement after treatment did not remain statistically significant for a full thirty days, another problem Sage blamed on the placebo groups.
Something weird: why did patients appear to do better with a lower dose? The difference wasn’t statistically significant, said Sage’s chief executive officer, Jeff Jonas, on a conference call. But he added: “The dose effect may not be in play” and that there was “almost a binary effect in these patients” – that is, once the drug started to work, increasing the dose had no additional effect.
Alfredo Fontanini, a Stony Brook University biologist who invested personally in Sage, says that he was convinced by earlier data that brexanolone, which is similar to a natural hormone called allopregnanolone, could be effective in post-partum depression. “The mechanistic rationale is well outlined in basic science papers and it translates well in clinic,” he argued. “It was great to see that it worked on the overall population.”
For Sage and its investors, big questions remain. One is whether a pill Sage is developing, Sage-217, will be as effective as brexanolone in post-partum depression. Another is whether that pill will prove effective in other disorders, such essential tremor, or, in the company’s biggest gambit, the more common form of depression, major depressive disorder.
Post-partum depression may be triggered by hormonal imbalances that brexanolone corrects. This is not as clear in major depression, Lieberman and I agreed. Jonas has taken a strategy of testing his drugs first in very tiny studies, which can give results that are way off by chance, under the idea that big positive results will be likely to translate once larger studies are done. This paid off today in post-partum depression, but failed spectacularly in a rare form of epilepsy in September. There, amazing case reports of patients who were saved by the drug did not translate into any improvement for those treated with brexanolone compared to placebo.
On his conference call with investors, Jonas said this result “Opens the door to a whole new way of treating mood.” Maybe. But we’ll all have to wait to find out what is behind it.
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64eafb537388122b581344489cc3501c | https://www.forbes.com/sites/matthewherper/2017/12/05/big-datas-top-breast-cancer-oncologists/ | 27 Top Breast Cancer Oncologists, Picked By Big Data | 27 Top Breast Cancer Oncologists, Picked By Big Data
What's below is the result of a challenge: can a company that helps patients find the right doctor identify the best physicians over all, or at least come close? (You can also go here for a list of top cardiologists.)
Last year, I wrote a magazine profile of a company called Grand Rounds, which aims to meticulously comb through data on physicians – everything from what they prescribe to the wait times in their parking lots—to match patients with the right doctor for them. The company’s founder, Owen Tripp, even used the service himself when a type of tumor was found in his ear. “It's not that there aren't good doctors, and it's certainly not that there aren't enough of them,” Tripp said last week at the Forbes Healthcare Summit. The problem is measurement.
OK, smart guy, I said. If you can tell which doctors are better, give me a list of the best. Grand Rounds uses a computer model based on publicly available and proprietary data, including administrative claims data from insurers, practice affiliations, board certifications, disciplinary actions, and academic publications. These data don’t tell how a doctor’s patients do, but they do allow the company to look at how doctors were trained, who they work with, what they prescribe, and procedures they perform. For instance, in breast cancer oncology, better physicians are more likely to perform genomic tests. In contrast, in cardiology, ordering more tests is a sign of lower physician quality. The lists we’re publishing today, in breast cancer oncology and cardiology, are the result of using a machine learning algorithm on many such measures.
There are limitations to this analysis. Grand Rounds says it misses excellent doctors who belong on it. Efforts to find outside experts who could vet Grand Rounds’ algorithms were unsuccessful. Like many efforts in machine learning or artificial intelligence, the results emerge from a black box that’s hard for outsiders to evaluate. And Grand Rounds is a private company, with the skepticism it entails. But this list, and the other, are at the least thought-provoking. And I can confirm, based on years of reporting, that many of the physicians included are indeed the best in their fields.
Honor Roll
Foluso Ademuyiwa Washington University in St. Louis Banu Arun MD Anderson Cancer Center José Baselga Memorial Sloan Kettering Harold Burstein Dana Farber Cancer Institute Saundra Buys Huntsman Cancer Institute, University of Utah Melody Cobleigh Rush University Medical Center Gabriella D'Andrea Memorial Sloan Kettering Elizabeth Claire Dees University of North Carolina Susan Domchek University of Pennsylvania Matthew Ellis Baylor College of Medicine Monica Fornier Memorial Sloan Kettering Kevin Fox University of Pennsylvania Lori Goldstein Fox Chase Cancer Center (Temple University) William Gradishar Northwestern Julie Gralow University of Washington Gabriel Hortobagyi MD Anderson Cancer Center Clifford Hudis Memorial Sloan Kettering Maryam Lustberg The Ohio State University Ann Partridge Dana Farber Cancer Institute Bhuvaneswari Ramaswamy The Ohio State University George Raptis North Shore-LIJ Cancer Institute Charles Shapiro Mount Sinai George Sledge Jr. Stanford University Medical Center George Somlo City of Hope Vered Stearns Johns Hopkins University Tiffany Traina Memorial Sloan Kettering Eric Winer Dana Farber Cancer Institute
Gallery: Breast Cancer Oncologists Honor Roll 28 images View gallery
Sarah Hedgecock and Ellie Kincaid contributed to this story.
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0437065d5751c30f5d4a7af34e11e295 | https://www.forbes.com/sites/matthewherper/2017/12/28/mourning-ben-barres-the-transgender-scientist-who-changed-neuroscience/ | Mourning Ben Barres, The Transgender Scientist Who Changed Neuroscience | Mourning Ben Barres, The Transgender Scientist Who Changed Neuroscience
Ben Barres, a neurobiologist at Stanford University's Medical Center, puts on a lab coat in his lab... [+] in the university's campus. (Photo/Marcio Jose Sanchez)
Ben Barres, a neuroscientist who established the importance of glial cells, which comprise 9 in 10 brain cells but had been dismissed as inconsequential, died on December 27. The cause was pancreatic cancer, according to a statement from Stanford University, where he was a professor and where he chaired the department of neurobiology until he was diagnosed last April.
“Ben was a remarkable person. He will be remembered as a brilliant scientist who transformed our understanding of glial cells and as a tireless advocate who promoted equity and diversity at every turn,” said Marc Tessier-Lavigne, PhD, president of Stanford University, in a press release. "He was also a beloved mentor to students and trainees, a dear friend to many in our community and a champion for the fundamental dignity of us all.”
Barres is remembered for his trailblazing scientific work, but also for the causes he fought for. He was openly and adamantly transgender, and was the first trans person admitted into the National Academies of Science. He was a tireless advocate for women in academia, and for his students. Professors often hold on to their students projects; Barre insisted they take those projects with them. He was a figure toward whom a great many other scientists felt a strong emotional bond. I found this out last night when I posted a link to Stanford's news release announcing his death on Twitter, and was blown away by the dozens of heartfelt responses.
"Ben was a giant and will be dearly missed," wrote Mary E. Hatten, the Frederick P. Rose Professor of Neurosciences and Behavior at the Rockefeller University. The Alzheimer's Drug Discovery Foundation added: "The pipeline of drugs in development for #Alzheimers owes so much to Ben Barres. He was a visionary scientist and generous mentor."
"My PhD was on glial cell biology and I referenced Ben extensively," wrote Greg James, a pediatric neurosurgeon in London. "He made a major contribution to our understanding that glia are not boring supporting cells but have a critical symbiotic relationship with neurons. He left us too young."
"I was lucky to have Ben Barres on my thesis committee," wrote Egle Cekanaviciute, a NASA biologist. "[I'm] forever grateful for being challenged & trained to defend my ideas, & inspired by his dedication to mentorship & inclusivity in science."
Hank Greeley, a Stanford law professor who focusses on biotech issues, wrote several tweets about Barres' life as a transexual. "We honor and miss him for his scientific greatness & his human goodness. But his identity & his constant support for trans people & issues were deeply important & not just to him," Greeley wrote, adding, in a second tweet: "[H]e was more than open, he was fiery about his identity and about trans opponents. We first met when he emailed me, a law prof, to ask about suing the Nat'l Academies Press about an awful book on trans people. ('No,' I said, & he listened.)"
Barres was an amazing speaker. I've included two YouTube videos of him speaking in this post, the first about science, and the second about his experience as a transgender man.
"To me, the thing about having a terminal disease, is, everybody knows they're going to die at some point," Barres says in the first video. "But to me the hardest part is this incredible time I've been having in science just comes to an end. There's all these questions I'm curious about, and I would be hiring new students and post-docs when I got sick, and I just told them all not to come."
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c27bc0cd3009b64cdbf7c9b3b3b3ffe5 | https://www.forbes.com/sites/matthewherper/2018/01/08/illumina-unveils-20000-desktop-sequencer-aimed-at-sequencing-germs/ | Illumina Unveils $20,000 Desktop Sequencer Aimed At Sequencing Germs | Illumina Unveils $20,000 Desktop Sequencer Aimed At Sequencing Germs
Illumina's new $20,000 iSeq 100 DNA sequencer. Illumina
Illumina, the dominant maker of DNA sequencers that are used in drug discovery, medicine, and biological research, is unveiling a new toy: A $19,900, one-cubic-foot box that puts DNA sequencing in the reach of many more scientists. Illumina is signaling it expects the device, called the iSeq Sequencing System, to be particularly useful to researchers studying viruses, bacteria, and other microbes.
"For under $20,000, any researcher can have access to the accuracy of an Illumina sequencer in their lab,” Francis deSouza, President and Chief Executive Officer at Illumina, said in Illumina's press release. “The iSeq 100 offers robustness and reliability for a broad range of applications ranging from germline and somatic tumor profiling to 16S microbial analysis and targeted gene expression.”
DeSouza is announcing the launch of the machine at the J.P. Morgan Healthcare Conference in San Francisco, which serves as biotech's big kickoff every year.
The press release also contains a quote from Pardis Sabeti, a researcher at The Broad Institute of MIT and Harvard who became known for her work sequencing the Ebola virus during the recent outbreak in Africa, saying the device "has great potential to transform infectious disease surveillance." She says that her lab will use it to focus on infectious disease monitoring, and the device's low cost and small size will allow researchers to use DNA sequencing where they most need it.
But the machine is itself evidence of how the fast the world of DNA sequencing is moving. Originally discussed a few years ago under the codename "Firefly," the new device was conceived as a competitor to devices made by Ion Torrent, which is now, after several mergers, part of Thermo Fisher Scientific. The Ion Torrent device used a CMOS chip, like the one in a digital camera, to sequence DNA. It had accuracy issues, but could fit on a tabletop. Illumina launched its own device, the MiSeq, to compete, which used Illumina's normal chemical and optical processes to sequence DNA.
The iSeq combines the two approaches, using both a CMOS chip and Illumina's normal sequencing-by-synthesis technology. The cost to prepare a sample for the box will range from $25 to $150, and Illumina promises "the same high resolution and accuracy of other Illumina sequencers," and it is half the price of the MiniSeq, which runs $50,000. A run of the machine takes 18 hours. The read length – the length of DNA sequence fragments that must be computationally reassembled – is 2 x 150 DNA base pairs.
But Elaine Mardis, a researcher at Nationwide Children's Hospital, was underwhelmed. "It's not that interesting," Mardis wrote via email. She says the $50,000 model she has basically does the same thing, but that what really matters is the costs of the reagents needed to do the sequencing, which are not mentioned. Besides, she says, Ion Torrent can deliver data on the same day, whereas the new device still needs to percolate overnight. The big problem for small labs, Mardis emphasizes, is analyzing all that genome data.
The new machine is also not an answer to another competitor, Oxford Nanopore. It has developed a portable DNA sequencer the size of a USB drive that gives very long reads but has much lower accuracy. The key utility of the device is that it can be used in difficult-to-reach conditions, at a low cost. A starter pack costs $1,000.
Illumina maintains its dominance at the high end of the DNA sequencing market, where machines can approach $1 million and the amortized cost of sequencing a human genome is about $1,000, a dramatic reduction from a decade ago that has powered a revolution in biotech research.
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d9d2350486250b9e4514f597b3d5a5b9 | https://www.forbes.com/sites/matthewherper/2018/02/07/why-a-gene-therapy-pioneer-is-raising-concerns-about-treatments-he-championed/ | Why A Gene Therapy Pioneer Is Raising Concerns About Treatments He Championed | Why A Gene Therapy Pioneer Is Raising Concerns About Treatments He Championed
James Wilson, gene therapy pioneer Jim Wilson
Jim Wilson has been one of gene therapy's pioneers. Now he's raising concerns about the safety of a technology he helped develop – at least when it is pushed to its limits. In two new studies his team conducted in monkeys, high doses of a certain type of gene were toxic.
"I recognize the fact that these are limited numbers [of animals], and in fact that studies were not designed to evaluate safety," Wilson says in an interview with Forbes, reproduced below. "But the fact is, we observed the toxicity with that limited number, which is, from my point of view, even more worrisome."
For decades, gene therapy – treating or curing sick people by replacing the worst parts of their DNA – has been a pipe dream. Now, it's a reality. Last year, the Food and Drug Administration approved gene therapies for forms of rare blood cancer, and a gene therapy to treat blindness.
All gene therapies rely on what scientists call "vectors" – which just means a way of getting DNA into a patient's cells. The most common vectors? Viruses. Hijacking cells to produce copies of themselves, after all, is what viruses do. And Wilson, the Rose H. Weiss Orphan Disease Center Director's Professor at the University of Pennsylvania, is the authority on vectors.
It's a hard-won expertise. In 1999, when it seemed that gene therapy was on the cusp of becoming a reality, a patient in a study Wilson was running died. The memory of that young man, 18-year-old Jesse Gelsinger, has motivated him to find better vectors. Gone is the widespread use of adenovirus, the vector used in that study. Wilson has become an advocate for another virus, adeno-associated virus, or AAV, which is used in many gene therapies including the blindness treatment Luxturna, approved by Spark Therapeutics.
That's why it shocked the gene therapy field when Wilson resigned as a scientific advisor to one AAV-focused firm, Solid Biosciences, just before the company went public, noting concerns about the safety of high-dose AAV. He says he can't talk about his relationship with Solid, but has published two different papers using two different versions of the AAV virus showing that it can have potentially lethal side effects used high doses in monkeys. For most uses (like blindness) these high doses aren't necessary. But for some conditions, like the muscle disorders Solid is targeting, they are.
Wilson spoke with Forbes at length about the results, and I'm publishing the bulk of the interview – edited slightly for length and clarity. "At the end of the day, the best we can do right now is to be as diligent as we can in non-clinical models to determine at what dose we would see benefit, and, similarly, at what dose we would see dose-limiting toxicity, and to select diseases in which the unmet need is so significant that it would justify the risks that, despite animal models, are largely unknown," he says. Read the interview below.
Matthew Herper: Before we get into the topic of this paper, let's talk a little bit about you. You've been a major player in this space. You've spoken very eloquently about the experience of treating Jesse Gelsinger, who died while being treated with gene therapy in 1999. How is that coloring the way you're thinking about the field now?
James Wilson: I've been focused on gene therapy for probably over 30 years. During that time, have assessed different vector technology platforms from those based on viruses and those based on non-viruses. What I did realize at the turn of the century, after the [ornithine transcarbamylase deficiency] trial and Jesse Gelsinger's death, is that we really needed better delivery vehicles, and that's what I focused my career on since. I believe that the technology of AAV that we now have is by far the best-in-class, and in the right circumstances, will be successful in treating patients.
MH: Let's get right to what you found, then, because you found what could potentially be a speed bump here in using that technology at least when you're using high doses of AAV.
JW: Most of the work that is underway in this field and almost all the work that we're conducting uses AAV vectors that are injected directly in the tissues or into certain compartments such as the retina or the central nervous system. There are a set of studies in the clinic that are based on injecting the vector into the blood after which it distributes broadly through many organs, but in particular, the liver. Those studies have formed the basis of some really exciting work in treating liver diseases such as hemophilia.
What we're talking about here, though, is an extreme example of the use of vectors to inject directly into the blood at very high doses in order to drive the vector into tissues that they otherwise do not penetrate, such as the skeletal muscle to treat inherited muscle diseases such as Duchenne muscular dystrophy, or into the brain to treat diseases such as spinal muscular atrophy.
We conducted two different animal studies in non-human primates and in pigs to study the efficacy of high-dose intravenous AAV to target the central nervous system. We did not expect to see any safety concerns because of the incredible safety track record that AAV has had. But what we indeed saw in both studies was that, at very high doses, the animals developed within the first few days after the vector was injected evidence for some liver damage and also activation systemically of inflammation, the consequences of which, was the development of a bleeding disorder or coagulopathy. What was surprising is this happened really in the first few days after the vector was administered. Now, in both studies, this resolved in some animals and they were fine. But in each case, one of the animals progressed to very significant disease manifested by shock, in one case, and severe hemorrhage or bleeding in the other that required euthanasia.
So this suggested that, selected at high enough doses injected in directly into the blood, that there is the potential for what we call dose-limiting toxicity. While we were surprised to see this because it hadn't been described, in retrospect it shouldn't be surprising because any biologic, if delivered at high-enough dose, will be associated with toxicity. I think what we've observed here is if that does occur, when injected at high dose, intravenously, these are the kinds of things that we would see. Therefore, these are the kinds of things that we should monitor for in the clinic.
MH: These are small numbers of animals. Couldn't this be the play of chance? Or could it be the animals that had the problems that had the coagulopathy or the shock were outliers in some way?
JW: I recognize the fact that these are limited numbers, and in fact that studies were not designed to evaluate safety. But the fact is, we observed the toxicity with that limited number, which is, from my point of view, even more worrisome.
In drug development, unfortunately, what often shuts down programs are the outliers. In this situation, really one out of three in the first study of the non-human primates, and three out of three of the piglets had the toxicity.
We've learned what the dose-limiting toxicities could be at high enough dose when injected intravenously. But what we have not learned is at what dose would this occur across multiple programs. I would caution anyone to directly extrapolate the dose at which we observe the toxicity in our study to that of another program.
Every lab measures the quantity of vectors used to dose differently. Those numbers can vary well over 10 fold. In other words, the monkey studies that were conducted at Audentes [Ed.: another biotech company] that support their gene therapy program in myotubular myopathy dosed the monkeys at eight times ten to the fourteenth copies per kilogram, which is a very high dose. The animals did fine and the company has proceeded with what appears to be the beginning of a successful clinical trial.
That does not mean that other vectors administered at that dose will be safe. On the flip side, if we saw toxicity at a dose of four times ten to the fourteenth copies per kilogram. That doesn't mean that you would expect to see toxicities at that dose in other programs as well.
MH: Why do you think these side effects occurring? You said you were surprised. Why are we getting these dose limiting toxicities? Do we have any idea of biologically what's happening?
JW: There are some data that the vector capsid, the shell of the viral genome itself, may be capable of activating what is called innate immunity. What we learned from the adenovirus trials was that it was the capsid of the shell that in some patients, under some circumstances, when injected systemically, would bind to immune-activating cells and immediately stimulate them to secrete inflammatory cytokines. In fact, our innate immune system has been designed to detect invaders and viruses, and the first response is the innate immune response. That's what I think we saw here.
MH: What was the specific goal of the study as planned? What were you testing?
JW: The first study in Human Gene Therapy was designed to evaluate efficiency of gene transfer in cells of the spinal cord and the brain using different routes of administration. There were a number of arms to the study that included directly injecting the vector into the cerebral spinal fluid, so-called intrathecal delivery using a variety of different approaches.
They were then compared to this arm of the study, which was to evaluate high dose systemic vector, which has been proposed by several groups as a way to get vectors delivered to the central nervous system. This was almost the control arm for the purpose of the study, which was to evaluate directly administering the vector into the brain.
The second study, in Molecular Therapy, was designed to evaluate the performance of a new vector that was published out of a lab in Cal Tech called PHPB, versus AAV9 for delivering genes to the central nervous system. In that paper, they described remarkable targeting to the brain with very low quantities of vector when administered intravenously in mice.
The goal of this study was to compare gene transfer to the brain based on an AV vector versus a PHP.B vector to determine whether the mouse data translated to monkeys. It didn't.
MH: But it sounds like you found the same dose limiting toxicity? What happened to those animals?
JW: Yes. In that study, we dosed animals at a modest dose, because they're monkeys, of AAV9 and PHP.B at doses that would be required to target the liver. But we did not see any enhanced gene transfer into the brain. Then we went to a higher dose close to that, but not quite, used in the first study. In there, the AAV9 animal had some lab abnormality but did okay.
But the PHP.B vector-treated animal developed within a few days the elevation in the liver enzyme and then the bleeding disorder or coagulopathy just like we had seen in the other animals. That animal had to be euthanized within the first five days of receiving vector.
MH: What would you advise companies -- or any researcher – to do differently now?
JW: Let me recognize that decisions to proceed into human studies are complicated. They're difficult decisions that need to be informed by the potential for risks that we have to concede are largely unknown, reconciled against the unmet need of the patients and the likelihood of benefit.
At the end of the day, the best we can do right now is to be as diligent as we can in non clinical models to determine at what dose we would see benefit, and, similarly, at what dose we would see dose-limiting toxicity, and to select diseases in which the unmet need is so significant that it would justify the risks that, despite animal models, are largely unknown.
MH: Is it possible that we could prevent these toxicities in patients, while still allowing them to try these experimental therapies?
JW: That's a really good question because I think it's an area that would definitely deserve some investigation. If our hypothesis is right, what we're seeing is the immediate activation of innate immunity. It reminds me of what happened with the CAR-T study recently where there was this sort of mass influx of T-cells, and activation of immunity, a systemic inflammatory response syndrome that had the potential to be lethal. That could have shut the program down, which would have been very unfortunate.
A group of investigators and various different labs determined that the way to prevent this from happening is, at the time the cells are administered, the patients are treated with an antibody to try to suppress the consequences of the inflammatory response.
If these kinds of toxicities begin to surface in the clinic, it would warrant studies to try to mitigate them through the administration of drugs at the time the vector is delivered to try to dampen or to suppress the inflammatory response.
Currently in the field, many clinical trials are including a short-term dose of corticosteroids at the time of vector administration. My hope is that there may be a cocktail of immune modulating drugs that could be administered at the time the vector is delivered.
MH: Could the toxicities be due to impurities in the vector preparation or anything like that?
JW: You can never rule out a contaminant contributing to an outcome when the product is made by cells. But the reason that I think it's unlikely in our experiment is that we saw the same kind of toxicity at similar doses in two studies in which the method of vector production and purification were very different.
MH: Why was there a difference in the toxicity between species?
JW: Our experience with vector-host interaction over the years with viral and non-viral vectors shows dramatic differences in the innate immune response or inflammatory response between animals. It's very hard to see in rodents, more severe in cats and dogs, and always the most extreme in primates. We have very limited experience in pigs, so I really don't know enough as to why the systemic and liver toxicity was not present in pigs versus non-human primates.
MH: Coming at this from another direction: why weren't these studies of dose limiting toxicity in these vectors done in primates until now? Normally, one of the things that you worry about a lot before a phase one trial starts is exactly this. It's finding that dose limiting toxicity.
JW: We've conducted studies in thousands of non-human primates, probably more so than almost the rest of the field. But we've never pushed the dose to these limits, so we would not have seen them before, based on the kind of work that we do.
Only a few programs, very few, are progressing their programs along a path of high dose systemic AAV. I suspect that the amount of experience at these doses is really low. Let me tell you another practical issue. It takes a lot of resources to make that vector. They're not experiments that are easy to do from a logistical or financial standpoint.
MH: Right. And, as you said, this doesn't relate to the hemophilia trials. It doesn't relate to the eye trials.
JW: The fact is that not many sponsors have proceeded down this path of very high dose vectors to target muscle or the brain. And it's not something that one would do unless you needed to create to a potential therapeutic. There's a limited database.
My view, and this is an hypothesis, is that any AAV factor, if pushed at high enough dose, is going to start to surface dose-limiting toxicity as we talked about. At which dose and where that will occur will vary from product to product.
We're really early in this game. I suspect others are going to begin to study this as we will begin to try to parse out what the mechanisms are. Understanding mechanisms even at the extreme can help possibly mitigate other problems that may occur. Maybe not with such dire consequences, but having said that, to do those studies, you need a lot of vector and you need access to non-human primates.
MH: We have human data in some of these dose indications, right. The AveXis product has been tried in humans. So far, we haven't seen these toxicities. Does that mean anything to you?
JW: I think it's a really important context that in the AveXis trial that they progressed 12 subjects, maybe more now, at those doses. That's encouraging for those programs. I would agree.
MH: Is there anything else you'd add here?
JW: In my 30-plus years in this field, I studied every viral vector that has been proposed, and early in my career and more recently, non-viral vector.
The safety profile of AAV with respect to immune toxicity is remarkable and qualitatively better than the experiences that I've had with other delivery platforms. That has not changed in my mind at all.
Most of the applications that are being contemplated, I still expect there to be a pretty good safety profile. However, if the doses get too high, I believe that there is the potential for dose limiting toxicity. I don't think anyone should be surprised by that. But let's not impugn the platform for what it is.
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62f0c66d5d082b86afd2c154e757f109 | https://www.forbes.com/sites/matthewherper/2018/03/26/ai-telemedicine-quantum-new-novartis-boss-says-tech-will-finally-change-the-drug-biz/?sh=27f788d56b54 | AI. Telemedicine. Quantum. New Novartis Boss Says Tech Will Finally Change The Drug Biz | AI. Telemedicine. Quantum. New Novartis Boss Says Tech Will Finally Change The Drug Biz
Global Head Drug Development and Chief Medical of Swiss multinational pharmaceutical company... [+] Novartis, Vasant Narasimhan. (AP Photo/Thibault Camus, Pool)
What does the youngest chief executive in Big Pharma want? A control room straight off the starship Enterprise.
When Vas Narasimhan, 41, took the helm of drug giant Novartis in February, he'd already put the project in motion. Novartis scouts were dispatched to visit air traffic control towers and the Swiss electrical grid to see how other industries dealt with torrents of data. Working with McKinsey's QuantumBlack unit, they built a software system called Nerve that not only keeps track of every data point on all 550 clinical trials testing Novartis drugs, but also uses analytic software to predict potential hiccups in the execution of those studies. Soon Narasimhan will be able to walk into mission control at the company's Basel, Switzerland, headquarters and call up whatever information he needs in an instant.
"When you look at history, it takes the medical establishment 50 to 75 years to actually change how we do clinical studies," Narasimhan says. "The first clinical study was done in 1670, the first placebo-controlled study in 1880, the first randomized controlled clinical trial in the 1940s. So now we enter a world where we do some things better than we used to, but fundamentally, we've not rethought how we do clinical trails. So we really approach it from the perspective of 'How could we use technology just to leapfrog many of the challenges?'"
This tech-focused perspective, and the will to change the way things are done, landed Narasimhan, an American, in the center seat at one of the world's largest drug companies. He's taking unprecedented steps to integrate artificial intelligence, telemedicine, automation and even quantum computing into the labor-intensive process of inventing new medicines and testing their efficacy and safety. The hope is that a young, charismatic chief executive can ignite Novartis shares, up just 12% in five years—underperforming rivals such as Pfizer, AstraZeneca and Merck, even as Novartis launched more new drugs than any of them. The company has been held back by manufacturing problems, slow sales at its Alcon eye-care division, and medicines that, while they sounded great, weren't embraced by doctors, patients or, perhaps most importantly, insurance companies. In 2017, sales grew 2% to $49 billion and earnings 12%, to $11.4 billion.
A tablet running Novartis' Nerve software, which gives executives real-time data on the company's... [+] clinical trials. Novartis
The drug industry has generally been skeptical of tech's potential. But the new CEO insists that "going big on data and digital" will be one of the keys to Novartis' future. "Our odds at Novartis of finding bad decisions, then making the right decisions, go up when we are powered by these machine capabilities and artificial intelligences." He's putting his own sweat into making that happen. The big question is whether he's right, or whether this is just a tech infatuation, and a distraction from Novartis' real mission: making drugs.
Narasimhan was raised in Pittsburgh, where his parents moved from India before he was born. Frequent visits back to see his grandparents shaped his worldview. He says his paternal grandmother received only a first-grade education, but most of her 11 children earned advanced degrees. So would Vas: first a bachelor's from the University of Chicago, then, from Harvard, both a medical doctorate (2002) and a master's in public health (2003). He spent three years working for McKinsey & Co., and joined Novartis in 2005. By 2009, he was running the company's U.S. vaccine business.
Joseph Jimenez, who helmed Novartis from 2010 until 2017, remembers hearing about the hotshot doctor. "He was a physician, but he was also proving to be successful running a commercial organization," Jimenez says. "Rarely do we find that combination of talent." (Narasimhan is currently one of only two M.D.s running a big pharma company.) Then there was the fact that Narasimhan was running the vaccines business while only in his 30s. "That said that this guy might have the talent to go all the way at the company," Jimenez says.
Novartis, with 120,000 employees globally and a staid Swiss heritage, has a careful process for picking rising stars. Narasimhan was being groomed, and was given the job of running an effort to make copies of biotech drugs—protein medicines like EPO for anemia or antibodies like the cancer drug Rituxan. But then Jimenez's head of development, the man in charge of running all the company's clinical trials, quit. Jimenez remembers running over lists of names, and coming on a list of dark horses, rising stars who hadn't been flagged for the job. "We all said, 'He's it.'" Narasimhan's belongings were on a container ship headed for Munich, where the generic division was based. Jimenez had it diverted to company headquarters in Basel.
Jimenez was himself was fascinated by the possibilities of digital technology. Novartis negotiated a deal with Verily, the life sciences arm of Alphabet, to create a contact lens that measures blood sugar levels and another with Microsoft to use a videogame system to assess the severity of multiple sclerosis symptoms. Narasimhan had marching orders to go after every cool tech project he could.
One was New York City's Flatiron Health, which tries to make data from electronic health records far more reliable. (So far, clinical trials with a placebo group give far clearer answers.) "We had met three or four times, and he knew the tech platforms that they work on, like what languages they're writing code in," says Nat Turner, Flatiron's 32-year-old chief executive. The company was sold to Roche, also based in Basel, but is still working with Novartis, too.
An obvious place computers could improve things: getting patients into clinical trials. A collaboration with Novartis is one of the few places that IBM Watson has actually shown it can move the needle, cutting the time it took to check to see if 90 patients qualified for a clinical trial from 1 hour and 50 minutes to 24 minutes. But Narasimhan gets even more excited about another approach. Currently, few patients enter clinical trials -- for instance, only 4% of those with cancer enter studies. Maybe the problem is that they're expected to travel to the doctors doing the research. What if you could bring the clinical trial to the patient?
That was the idea behind Science37, a Los Angeles startup that uses telemedicine to send medicines and nurses to people's houses. Its founders thought initially that the effort would work mainly with pills, but are finding patients will inject medicines, too. Novartis was one of the original investors, and earlier this month pledged that it would start ten trials with Science37 over the next five years: "Technically, I think he's younger than me, but I really look up to [Vas] as a mentor," says Noah Craft, 46, Science37's chief executive. "He's quite a visionary as to how he thinks about shaping the organization. He's also a really interesting human to talk to in life."
Sometimes, the treatments themselves might be software. Also in March, Novartis partnered with Pear Therapeutics to develop programs to help patients deal with schizophrenia and multiple sclerosis symptoms. But where Narasimhan sees real potential is in using software to invent drugs. Novartis is already using an artificial intelligence system called "the digital cortex" at its Cambridge, Mass.-based research laboratories to predict what medicines may work even before they start clinical trials. Narasimhan is also keen on the possibility of using quantum computing, which uses the strange physics of subatomic particles to get extra computing power, to speed up the difficult process of taking a molecule that seems to sort of work and turning it into a medicine that will have a chance once it reaches the market.
The point of all this reimagining? Novartis' labs are productive, having launched 16 drugs over the past decade, more than any other company, according to the Innothink Center for Research in Biomedical Innovation. But Narasimhan says he wants Novartis to make "smart, contrarian bets," like the company's 2012 licensure of what became Kymriah, a treatment that genetically reengineers white blood cells to attack cancer, or its test of rare disease drug canakinumab, to treat heart disease by reducing inflammation. There's controversy around both—Kymriah costs $475,000 a year, and it's not clear that canikinumab will be marketed to prevent? heart attacks. But Narasimhan's point is that he doesn’t want to be in a crowded market, where many companies are trying to develop drugs that are essentially the same. He wants to be way ahead—and in left field.
He knows he has other problems. He defends Kymriah's price as cost-effective, especially when the refund policy Novartis is trying to negotiate with insurers is thrown in. But he admits the drug industry, widely admired in the 1980s and 1990s, is not so widely admired now. "We lost that because of decisions we've taken over the last 20 years, in terms of how we've promoted our medicines, and how we've priced our medicines, how we take price increases," he says. He thinks by making the right decisions and developing the right medicines, he can slowly win back the public's trust.
"I would say it's a long road, and that's not something I'm going to see," he says of drug companies improving their reputation. "I'm a young man. I'll do my best during my term."
The Eureka Score These pharma firms had the most drugs approved between 2008 and 2017. Company Number of drugs approved Novartis 16 J&J 15 GlaxoSmithKline 14 Hoffmann-La Roche 12 AstraZeneca 10 Merck&Co 10 Pfizer 10 Source: Bernard Munos, Center for Research in Biomedical Innovation.
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a1c9d5ea40550db94bd620e440b2c7a8 | https://www.forbes.com/sites/matthewherper/2018/05/23/freenome-sets-sights-on-blood-test-to-detect-colon-cancer/ | Freenome Sets Sights On Blood Test To Detect Colon Cancer | Freenome Sets Sights On Blood Test To Detect Colon Cancer
Freenome chief executive Gabriel Otte Freenome
Freenome, a Silicon Valley startup aiming to develop blood tests to detect cancer early, is choosing its first product: a test to detect colon cancer.
The company was founded by Chief Executive Gabriel Otte and Chief Operating Officer Riley Ennis when both were still in their 20s. (They were on Forbes 30 Under 30 list in 2017). It has raised $77 million from venture capital firms including Andreessen Horowitz and Section 32. In another field that would be a lot of money, but it's competing with GRAIL, the spinout of DNA sequencing firm Illumina that has raised $1.5 billion in private money, and Guardant Health, which is spring-boarding off an existing test used to select treatment for patients diagnosed with advanced cancer.
What makes Freenome different is that instead of looking only for circulating DNA from tumors, as other firms are doing, the company is looking at other chemicals in the blood that may mark a tumor's presence, too. It detects patterns in all these chemicals using artificial intelligence.
Colorectal cancer is neither the deadliest cancer nor biggest unmet need. But it is a better-travelled path for a diagnostic test company. "It's the right stepping-stone for a company like ours given the regulatory and reimbursement hurdles," says Ennis, the COO. Adds Otte, the CEO: "Anybody who has lived in this space would tell you that reimbursement is problems number one, two, three, four, and five."
Freenome is announcing its first clinical validation study for its colorectal cancer blood test, and is modeling it on the clinical study done previously by Exact Sciences for its Cologuard test, which is used to screen for colon cancer by checking for DNA in stool. It is even hiring the same clinical research organization, Health Decisions, that ran Exact Sciences' study. The study will involve 3,000 patients between the ages of 50 and 84 who are at average risk of colorectal cancer. If the study is positive, it is expected that a second study will be needed to secure approval from the Food and Drug Administration.
Otte found himself in hot water last year when Buzzfeed reported that he had portrayed himself as having a Ph.D. when he, in fact, did not have one. He apologized in a Medium blog post in which he called the misimpressions "inadvertent" but "inexcuseable." He says that since then, he has learned a lot by learning on mentors that include Anne Wojcicki, the 23andMe founder and a Freenome investor, and Michael Pellini, who previously ran genomics testing company Foundation Medicine.
As the new study is progressing, Otte and Ennis are also taking another step: hiring a chief commercial officer, Mike Nolan; he's also coming from Foundation. Otte says it took nine months to find Nolan. "By me being here now, we can take a stepwise deliberate approach in the market," Nolan says. "What we are aiming to do is remarkable. We need to have credibility, and we need to be inspiring."
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75f03f66b85b8e1ab1c73efc92f92abf | https://www.forbes.com/sites/matthewherper/2018/09/20/for-a-new-device-to-treat-maternal-bleeding-a-young-entrepreneurs-big-step-was-letting-go/ | For A New Device To Treat Maternal Bleeding, A Young Entrepreneur's Big Step Was Passing The Torch | For A New Device To Treat Maternal Bleeding, A Young Entrepreneur's Big Step Was Passing The Torch
Jessie Becker co-founded Alydia Health in 2011. Alydia Health
This morning, Alydia Health, a tiny Menlo Park, California, startup cofounded by a 21-year-old woman, announced that it has secured $10 million in funding to test a medical device to prevent mothers from bleeding to death after childbirth.
Maternal death has long been seen as a problem of the developing world, but it has become a concern in the U.S., too. In 2000, the United Nations set a global goal of reducing maternal mortality by 75% by 2015, compared with 1990. Instead, in the U.S., the rate of maternal deaths increased 80%, to 18 deaths per 100,000 births—meaning 700 American mothers die annually because of childbirth.
"We have struggled with hemorrhage," says Mary D'Alton, the chair of the department of obstetrics and gynecology at Columbia University Irving Medical Center. "I thought, what a novel way to think about it. I felt, because of the vexing problem of hemorrhage and the difficulty of moving the needle and the fact that we had very few new treatments for hemorrhage, this would be an important tool to investigate."
D'Alton will be leading a 111-patient clinical trial conducted at multiple sites across the U.S. to test Alydia's device. The study will be funded with the money being raised today, which is coming from investors including the Global Health Investment Fund, an impact investment fund structured by J.P. Morgan and the Bill and Melinda Gates Foundation, and Astia Angels, a global nonprofit aimed at leveling the playing field for women investors.
The credit for the fundraise, and a study that could result in approval from the Food and Drug Administration, goes to Alydia's chief executive, Anne Morrissey, 52, a veteran device executive. The credit for hiring Morrissey, though, goes to a cofounder of the company, Jessie Becker, now 28.
Becker cofounded Alydia, until now known as InPress Technologies, as a student at Cal Poly as part of a startup competition in 2011. The prototype device, designed by bioengineering students, tries to mechanically reverse the natural processes that can lead to a uterine hemorrhage. One of the problems in uterine hemorrhage is that the uterus stops contracting normally. Right now, doctors try to treat this problem with drugs that cause the uterus to contract or by inserting another surgical device, a balloon made by Clinical Innovations, a private-equity based company in Utah. If those options don't work, the next step is a hysterectomy.
Instead, the Alydia device uses a silicone loop (it has a texture like a baby pacifier) and a wall vacuum to use suction to close the uterus. "It puts the uterus in a position that when it is ready to contract on its own," says Morrissey. Becker and her cofounder, Nathan Bair, moonlighted until 2013, when the company was taken in by the Fogarty Institute, the incubator run by surgeon and medical inventor Thomas J. Fogarty. Becker raised $1.3 million in seed money. She was featured on Forbes' 30 Under 30 In Healthcare list in 2015.
Anne Morrissey, Chief Executive of Alydia Health, far right, with most of her 8-person team. Alydia Health
Becker says raising money as a 22-year-old with no medical device experience was tough. It was Fogarty himself who made the introduction to Morrissey. He had run into Morrissey while she was serving as the chief executive of a consumer company aimed at supporting food waste recycling, a big step away from her history in medical device sales. "I really miss women's healthcare," she told Fogarty. "There's someone you should meet," he replied.
During their first meeting, Becker says, Morrissey critiqued her pitch deck for raising money from investors. Becker and her cofounders were squarely focused on developing their product for the developing world. The obvious pitch was to use it in the U.S., where there is a more obvious market. Becker protested, and Morrissey listened. They ended up in the middle: The U.S. is the first market the company is focusing on, but it is still committed to making sure women around the world—in the company's words, "from Sub-Saharan Africa to New York City"—can get the device. That commitment ended up being important for fundraising, too: The Global Investment Fund focuses on technologies that could have an impact on the developing world.
In a pilot study of 10 patients conducted in Indonesia and published in Obstetrics and Gynecology, the Alydia device stopped bleeding in all patients within 2 minutes. Morrissey says that the device has been tested in another 18 patients with similar results.
The 111-patient study the company is conducting, with input with the FDA, will not have a control group. Instead, it will compare the data with published data on the balloon device. D'Alton says that a trial comparing the two may be worthwhile down the road, but simply studying the device in clinical practice seemed like the most prudent step. That will not be rigorous enough for some medical experts, but it will likely satisfy the FDA if the results are positive. The balloon device, D'Alton says, has not been tested in a controlled trial either.
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564c6c2b6a012bc42a61ea8cc498ea1e | https://www.forbes.com/sites/matthewherper/2018/09/28/crispr-based-drugmaker-raises-80-million/ | CRISPR-Based Drugmaker Raises $80 Million | CRISPR-Based Drugmaker Raises $80 Million
DNA replication Getty
KSQ Therapeutics, a Cambridge, Massachusetts-based biotechnology company that uses the genetic-engineering tool CRISPR to develop new drugs, has raised $80 million, its second big fundraise in as many years. KSQ raised $76 million last October.
Instead of using CRISPR to try to modify DNA to treat disease, as companies like Editas and Intellia are doing, KSQ makes modifications as a way of looking for genes that may produce proteins that would be useful drug targets.
KSQ's chief executive, David Meeker, says he's well aware of the long odds of drug discovery. Only 2 in 100 medicines that are tested in the lab make it to the market; only 1 in 10 that starts clinical trials reaches patients. "What I love about KSQ and the whole space of immuno-oncology is you do have a shot at the miracle," Meeker says.
The company is working on 12 different drug discovery programs in three areas: adoptive T-cell therapies, in which modified white blood cells are used to treat cancer; immuno-oncology, in which drugs are used to augment the immune system so it can fight tumors; and targeted therapies, which leverage genetic weaknesses in cancer cells.
The T-cell program could enter human tests in 2019, and the first data from patients could emerge the next year. Meeker emphasizes that with a program like that, he's looking for dramatic effects. Another promising result, he says, is a CRISPR-screen of immune-system-based targets. It picked up the gene for the programmed cell death receptor one (PD-1), the target of the blockbuster drugs Keytruda (from Merck) and Opdivo (from Bristol-Myers Squibb), but also other targets that could result in new medicines.
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Cofounded by 2017 30 Under 30 list member Tim Wang, then a graduate student at MIT, and now run by former Sanofi Genzyme CEO David Meeker, the company is also announcing that its platform, which they’ve dubbed “CRISPRomics,” has developed a pipeline of 12 new oncology drug discovery platforms across three oncology drug categories—targeted therapies, immuno-oncology and adoptive T-cell therapies.
KSQ was cofounded in 2015 by Timothy Wang, who was featured on Forbes' 30 Under 30 in Healthcare in 2017, along with William Hahn of the Broad Institute and the Dana-Farber Cancer Institute, David Sabatini of the Whitehead Institute and MIT, Jonathan Weissman of UCSF and funding from Flagship and Polaris.
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e6f48ab19e345807ac6031993c96197b | https://www.forbes.com/sites/matthewherper/2018/11/20/is-amarins-fish-oil-derived-drug-a-historic-breakthrough-or-not-its-complicated/ | Is Amarin’s Fish-Oil-Derived Drug A Historic Breakthrough Or Not? It’s Complicated | Is Amarin’s Fish-Oil-Derived Drug A Historic Breakthrough Or Not? It’s Complicated
Vascepa is not just any fish oil, and is different from over-the-counter supplements. Here's a ... [+] picture of a salmon jumping over the Goldstream River. Getty
Cardiologists are still grappling with clinical trial results released last week that showed that Vascepa, a fish-oil-derived drug, reduced heart attacks, strokes, and deaths from cardiovascular disease by 25% in patients who had elevated triglycerides, or particles of fat in the blood. Views range from “healthy skepticism” to a hope that the study could rank among the most important ever in cardiology.
The apparently astounding benefit was paired with a number of caveats that some doctors worry could have inflated Vascepa’s apparent benefit, including a mystery as to exactly how the medicine works, a placebo that could have hurt patients, and previous studies of lower doses of similar fish oil drugs that were resoundingly negative. (Vascepa is a purified form of eicosapentaenoic acid, or EPA, a component of fish oil.) Some top researchers have visibly struggled with the results. The drama has been accentuated because Amarin Pharmaceuticals, Vascepa’s maker, is a small company with a devoted following of vocal individual investors.
How much can a doctor’s opinion shift on these data? When the headline results were released by press release in September, Sekar Kathiresan, director of the Cardiovascular Disease Initiative at the Broad Institute, at first reacted to the news by saying "Wow!" When he saw the results as published in the New England Journal of Medicine, he worried about exactly how the drug was working and said he was "probably a little too enthusiastic with my initial comment." But he now thinks his initial reaction was probably right, and that the Vascepa results constitute a major advance.
James Stein, Robert Turell Professor of Cardiovascular Research at the University of Wisconsin, is a skeptic, believing that the placebo group in the study probably raised cardiovascular risk, making Vascepa look better than it was. But he’s still planning to try Vascepa in some patients. “I don’t know how much to discount its effectiveness,” Stein says. Even if he assumes that half of the effect was from the placebo, the benefit is still better than moving from a low dose of atorvastatin, the popular cholesterol drug, to a higher one. He doesn’t plan to prescribe the drug (or other fish oils) to people on anti-clotting drugs like Plavix, though, because it may increase the risk of bleeding. “That’s where I am today,” he says.
In an editorial that accompanies the study’s publication in the print edition of the New England Journal of Medicine, John J.P. Kastelein and Erik S.G. Stroes of the Academic Medical Center, University of Amsterdam, write: “We welcome these results with surprise, speculation, and hope.” They express concern that the data aren’t explained by Vascepa’s expected mechanism of lowering triglycerides, that the result conflicts with previous trials of fish oils and that the placebo group may have had an effect. Kastelein is among the researchers conducting a 13,000 patient study of Epanova, another fish-oil-derived drug manufactured by AstraZeneca.
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Should doctors use Vascepa? “They should use it,” Kastelein wrote via email. “The only thing we are waiting for is to learn whether Vascepa is unique or other fish-oil preparations or other doses of EPA have less, similar or better efficacy.”
Not everyone is so sure. “I have what I would say is some healthy skepticism about the results,” says Eric Topol, the Gary & Mary West Endowed Chair of Innovative Medicine, Scripps Research. The main reason, he says, is that the study doesn’t fit with the many other studies of lower doses of fish oil preparations that have shown no benefit. Another worry, he says, is that triglyceride-lowering does not seem to explain the cardiovascular benefit that was seen. “That is distressing,” he says, “because we have no idea what the mechanism is. The assertion that it’s just because of high EPA dose or pure EPA—that’s all speculation.”
Topol also has concerns that the placebo may have raised cholesterol and c-reactive protein. “They happened to have a placebo that’s not inert,” he says. That won’t explain the results, he says, but it’s also not helping to sort things out. He says he’s not comforted by an analysis showing that the results hold up when researchers analyzed them with just the patients in the placebo group whose low-density lipoprotein (LDL, the "bad cholesterol") went up, or just those in whom LDL stayed flat. “That’s just one way of looking at it,” he says. “It probably should be looked at in multiple ways." Still, he says, "At the end of the day, I don’t think that the main explanation is that the placebo is the problem. I doubt it was the singular problem. It was contributing.”
“There’s too many warts here to make [it seem] that this is pure triumph,” Topol says. “There’s some things that just don’t compute.”
Other top cardiology researchers had far more positive views. Jane Armitage, an epidemiologist at the Nuffield Department of Population Health at Oxford University, writes via email that it is “very unlikely that the small dose of the placebo oil is likely to have caused any problem, although it is slightly odd that they chose a mineral oil rather than a vegetable oil.” She argues the results are “believable in light of the prior evidence.”
Unlike other experts, who largely believe that Vascepa’s effects must go beyond lowering triglycerides to preventing cardiovascular disease in other ways, perhaps by reducing the risk of sudden cardiac death or clots, Armitage believes that the 44 milligram per deciliter drop in triglycerides seen in the study could explain the benefit. She points to a 2011 analysis of multiple studies of fibrates, a different type of triglyceride-lowering drug, which showed a similar benefit in patients with high triglycerides. Other fish oil trials probably failed because they used much lower doses. “It seems that high doses of fish oils are needed to gain benefit at least in this high triglyceride population,” Armitage writes.
Even most proponents of the argument that the placebo in the study was harmful doubt that it increased the rate of events more than 5%; it’s the lack of a clear understanding of how the drug is working that bothers them most. But Rory Collins, the head of the Nuffield department at Oxford, argued in an email that other factors could explain the increase in cholesterol seen in the placebo group. One factor is that low cholesterol was required for patients entering the study. That could have meant that researchers were picking people at what was a low cholesterol level for them, and the levels simply returned to normal. (This is called regression to the mean.) It also could be the result, he says, of statistical quirks because the tests weren’t collected in random order—an effect that researchers could test for by going back to banked blood samples.
“An effect of the mineral oil remains a possibility, but my guess would be that it is largely if not wholly an effect of the high-dose EPA through mechanisms beyond merely lowering [triglycerides],” Collins writes. He poses a provocative question: What if the Vascepa study, called REDUCE-IT, is to EPA what a 1995 study called 4S was to cholesterol-lowering drugs called statins? The 4S study, also known as the Scandinavian Simvastatin Survival Study, was funded by Merck and released in 1994. It was the first study to show that a cholesterol-lowering statin drug prevented heart attacks and, indeed, saved lives in patients who already had heart disease. It started years of debate, and the drug used in the study, Zocor, was surpassed by rival medicines made by other companies. But statins become one of the most popular classes of drugs the world has ever seen, generating hundreds of billions of dollars in sales and saving countless lives.
It’s a question, not an answer. In recent years, new cardiovascular drugs have been commercial flops even when they seemed like scientific successes. But it is a tantalizing possibility.
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be21e2506452f9bf947e52cd233a4542 | https://www.forbes.com/sites/matthewherper/2018/12/10/buzzy-startup-10x-genomics-buys-spatial-transcriptomics-in-bet-on-genetic-tools/ | Buzzy Startup 10x Genomics Buys Spatial Transcriptomics In Bet On Genetic Tools | Buzzy Startup 10x Genomics Buys Spatial Transcriptomics In Bet On Genetic Tools
10x Genomics Chief Executive Serge Saxonov: "“We generally understate how little biology we, the ... [+] world, know.” 10x Genomics
10x Genomics, a buzzy, closely held genetics startup based in Pleasanton, Calif., is purchasing Stockholm-based Spatial Transcriptomics for an undisclosed sum in a bid to add another type of genetic imaging tool to its fast-growing line of products.
The company was founded in 2012 by Chief Executive Serge Saxonov, the founding director of research at 23andMe, and Chief Scientist Ben Hindson, who founded startup QuantaLife, which was sold to Bio-Rad for $162 million in 2011. 10x says it had annual sales of $71 million last year and that sales will be significantly higher this year. It has raised a total of $208 million from investors including Venrock, Fidelity, and Meritech Partners, according to Pitchbook, including a $125 million fundraising in April that valued the company at $925 million.
“We generally understate how little biology we, the world, know,” says Saxonov. “We know only, kind of, slivers. The best way to accelerate our understanding of biology is to build new tools.”
10x’s business so far has been built on that premise. Most genetic research is done by taking DNA from multiple cells, which may have tiny differences between them. But 10x sells tools that biologists use to understand the genetics of individual cells: both what genes are coded in their DNA and which genes are being used by the cellular machinery of each individual cell. The company’s product can also be used to pick up immunological differences at the cellular level.
Saxonov says that he believes the Spatial Transcriptomics technology could be equally useful to researchers, and equally lucrative for 10x. Developed at the Science for Life Laboratory in Stockholm, Sweden, it combines DNA sequencing and microscopes to look at varying genetic activity as something that changes from place to place among a group of cells. Spatial Transcriptomics will continue to operate in Stockholm. Meanwhile, 10x is also moving to new digs in Pleasanton, quadrupling its presence in the city and adding 200 new positions. Saxonov says 10x plans to hire in “every function” of the company.
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0988264dc70018c328e9c44458216191 | https://www.forbes.com/sites/matthewherper/2018/12/17/fda-names-flatiron-health-executive-amy-abernethy-deputy-commissioner/ | FDA Names Flatiron Health Executive Amy Abernethy Deputy Commissioner | FDA Names Flatiron Health Executive Amy Abernethy Deputy Commissioner
Amy Abernethy, chief medical officer of Flatiron Health, sits with Robert Califf, at a company event ... [+] early this year. Flatiron Health
The Food and Drug Administration has named Amy Abernethy, currently the chief medical officer at Flatiron Health, a unit of the drug giant Roche, to one of its highest positions. She will start in a few months.
Abernethy, an oncologist who is credited with helping Flatiron transform data collected from electronic medical records into information that might become acceptable to FDA regulators, will be the Principal Deputy Commissioner for Food and Drugs. This is the highest position at the FDA that is not a political appointment. It cuts across all areas of the agency’s remit, overseeing initiatives that cut across offices that oversee the regulation of drugs, medical devices, tobacco and food. Flatiron was purchased by Roche at a valuation of $2.1 billion earlier this year. That potential conflict of interest could be an issue for some outside the FDA.
“She’s a highly regarded thought leader who has held numerous positions of leadership in her fields of interest and distinguished herself for her intellect, her passion for patient care and science, and her collegiality,” Scott Gottlieb, the FDA Commissioner, wrote in a memo to FDA staff announcing Abernethy’s appointment. Robert Califf, the previous FDA commissioner and a mentor of Abernethy’s, echoed Gottlieb’s praise. “In my wildest dreams, I wouldn’t have imagined Scott could come up with somebody this highly qualified,” Califf said. “So I think it’s really good for the country. I’m really excited about it.”
Abernethy says that the role was too meaningful to pass up. “I had always thought I would go into government service, and I have always believed that one of the ways you make change is through policy and regulation,” she says. She hopes to work on speeding up the collection of data that can be used in clinical trials—“Historically, patient-defined concerns were always secondary, and the question is: How do you make the needs of the patient the obvious thing that we’re working on?” she says—and on making sure patients get the right treatment at the right time, including by using more genetic tests, an idea known as precision medicine. “The more we have precision medicine the more it means we stop doing things that don’t work,” she says. But she also acknowledges that the role is broad, and that she may end up working outside her specific plans. “This is not my chance to solve the set of problems I think are important,” she says. “It’s a chance to spend 100% of my time solving problems that are important for human health.”
Abernethy’s research has often focused on answering questions industry had little financial incentive to address. A 2010 study, financed by the National Institutes of Health, showed that in 239 patients with shortness of breath, breathing from an oxygen tank was not superior to simply breathing the air in their rooms. Much of her work has focused on imagining how getting data from patients in real-time could allow the healthcare system to “learn” more quickly, leading to better care. That led her to work, initially, with the American Society of Clinical Oncology to create a data network, and later to her role at Flatiron Health. Flatiron has a business model of using data from patient health records to create research that can be useful to pharmaceutical companies. But one of Abernethy’s major recent papers showed something that wasn’t that flattering to companies like Roche, which also owns a firm that does genetic cancer testing, Foundation Medicine. Patients that got tests like Foundation’s lived no longer than those who didn’t in Abernethy’s study, largely because doctors rarely prescribed a different treatment based on the test result. At Flatiron, Abernethy also continued to push for other ideas: a 2017 editorial in Nature Reviews Clinical Oncology, argued that there was more need to ask patients, in a structured way, how they are feeling.
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For Flatiron, which is just starting to see the FDA consider the use of its data and to gain traction with pharmaceutical companies, her departure will represent a challenge. The company was featured in a November cover profile in Forbes.
“It’s bittersweet,” says Nat Turner, Flatiron’s cofounder and chief executive. “She had a lot to do with this. We’re really excited though. The FDA—I think if she had gone anywhere else it would have been tougher, but the FDA is so central to what we do at Flatiron because real-world evidence is so key to what we do, there are just so many opportunities to advance the ball.”
Turner clarified that he’s certain that Abernethy’s work will have nothing to do with Flatiron directly. But her tenure is likely to be shaped in part by how the FDA chooses to deal with the potential conflicts of interest raised by her most recent role.
An FDA official at Abernethy’s level would rarely make decisions that directly impact any single company. But she will be involved in shaping larger regulations that will impact how data collected from clinical practice, called “real-world evidence” by researchers, can be used. In his memo to staff, Gottlieb, the FDA commissioner, said that Abernethy’s ethics review is still pending. It will likely help that she is unlikely to own large amounts of stock in either Flatiron or Roche, because Roche paid for Flatiron in cash.
Abernethy says she plans to be proactive in dealing with those issues. She compared her expertise in the use of data to being an expert in the biology surrounding a particular drug. A conflict, she says, does not erase the expertise. “I happen to be a methods expert in data, that is what my expertise is in, full stop. As the issue is how to use data, you would argue that Flatiron is a data company and FDA is a data agency.” Still, she says, the exact rules regarding what she will and won’t do at the FDA have not been set. She says: “I will follow the rules.”
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be75af0fc0a16184535b4dd50668df0c | https://www.forbes.com/sites/matthewherper/2018/12/21/what-can-you-do-for-your-loved-ones-when-youre-dying-of-cancer/ | What Can You Do For Your Loved Ones When You’re Dying Of Cancer? | What Can You Do For Your Loved Ones When You’re Dying Of Cancer?
“Just remember data always has a face.”
That was the advice that Michael Becker, a former biotechnology company chief executive who now has head and neck cancer, told the assembled executives at the Forbes Healthcare Summit in New York last month. Behind every data point in every spreadsheet, there is a human being, he said. “There is a person like me, there’s a person with a family, there’s a person with children, there’s a person who has been touched by that disease.” Both he and the audience were choking back tears.
Becker, who I profiled earlier this year, developed a cancer caused by the human papilloma virus, or HPV. Usually such cancers are highly treatable. But his returned after six months. It is likely that it will eventually kill him. “One thing I decided,” he said, “is I wanted to do something that mattered.” For him, it was blogging about his experience, both to raise awareness that HPV vaccination can prevent cancer, and to talk about what it means to die.
“I really think we need to start talking about dying,” Becker said. “Even though a patient might be in pain or bedridden or terminal, they still have goals that matter, they still want to make their mark on the world, maybe even more so because they don’t have much time to do it.”
And it was that topic that went on to resonate. The session after Becker’s talk featured big names in health care who had all taken care of loved ones as they died of cancer. Becker had a question for Lucy Kalanithi, whose late husband, Paul Kalanithi had chronicled his own lung cancer in the bestseller When Breath Becomes Air. Pulling himself together, Becker asked a question about his wife. “Is there anything I can do to make her life easier?”
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“Paul said, ‘You were more than enough. Just so you know.’ And I hold on to that,” Kalanithi said. She also talked about knowing the limits of what a caregiver can do. As a physician herself, she felt a huge responsibility to help Paul avoid overly aggressive care that might be traumatic, but not helpful. And they discussed what he wanted a lot. But one day, he said to her: “I just want you to know, in case it ends up being really traumatic, for me, or you, or I’m getting CPR and you don’t think that’s supposed to happen: The last day of your life is not the sum of your life.
“The last day of your life is the last day of your life,” Paul Kalanithi told his wife. “And the sum of your life is the sum of your life.”
Paul’s words, Lucy said, absolved her from future guilt. It was simply saying those words that mattered. Other panelists agreed. Peter Bach, a researcher at Memorial Sloan-Kettering known for his work on drug pricing, spoke about losing his wife to breast cancer. A few days before she died, she told him: “I feel incredibly lucky.”
“I have carried that with me since that moment,” Bach said. “It’s absolving in some way. Because it’s very easy to sit here and say, for me, my biggest regret is everything she’s missed. But I chose to believe her, and think it was true what she was telling me.”
Christi Shaw, an President, Lilly Bio-Medicines, a division of Eli Lilly, cared for her sister, who had multiple myeloma. To do so, she’d quit a job at the drug giant Novartis. Her sister died suddenly, after she fell in her home and had a subdural hematoma because her blood would not clot. But she had left Shaw a note: “You did so much for me, and we got so much more time together.” Their stories were reminders that medicine is about human beings, and that we all need to be cared for and to care for our loved ones. At an event that often focused on the science of business of healthcare, it was the most powerful moment of the day.
Lucy Kalanithi talks about "Healthcare from the Outside In" at the 2018 Forbes Healthcare Summit. Victoria Engblom
A personal note. After almost 19 years covering health care at Forbes, I’m leaving for a new adventure as a writer. This will be my last post here.
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cc8a4240acddc04765cc17d1d0cc0d4d | https://www.forbes.com/sites/matthewhulbert/2012/09/29/president-putins-growing-gas-insanity/ | President Putin's Growing Gas Insanity | President Putin's Growing Gas Insanity
Einstein once said the definition of insanity ‘is doing the same thing over and over again, and expecting a different outcome’. By most counts, that makes Gazprom and President Putin, pretty insane. They’ve spent the last decade trying to sell gas into China, and repeatedly failing to do so by sticking to the same old pricing grounds: no matter what Moscow says, China won’t pay oil indexed prices for Russian gas. How many times Putin needs telling before the penny drops, no one knows…
Asylum Central
The latest bout in the asylum came last week when Gazprom jetted over to Beijing to progress gas agreements, albeit with a twist. Rather like 2009 when Russia got China to stump up a $25bn ‘loan for oil agreement’ to finance the Rosneft / Transneft ESPO pipeline to the Chinese mainland in return for 300,000b/d supply over twenty years, Gazprom is applying a similar formula for the proposed Altai gas pipeline. Gazprom’s growing capital constraints undoubtedly make this a virtue borne out of necessity for the Russian gas giant, but it wants China to provide 40% upfront costs to build the $14bn pipeline. It would be no mean feat given it would span around 3,000km across Russia, Kazakhstan, Mongolia and into China, hooking up with the West-East gas pipeline in the Xinjiang region.
But the problem (quelle surprise) is that Russia still appears unwilling to offer the kind of discounts China wants to sign on the line. Tepid memoranda of understanding drafted between the two nations in 2006 look likely to remain exactly that. Russia wants to yield $350-$400 per 1,000 cubic metres for its gas (i.e. oil indexed prices), while China is pitching a $200-250 price range (little more than they’d pay for coal in equivalent terms).
Unfortunately for Russia, its snags actually go far beyond mere pricing. The Chinese have totally outsmarted Moscow by keeping Russia on the hook, all while landing major supply side fish in Central Asia, Australasia, Southeast Asia, the Middle East, and even North America. That’s before we consider 100bcm domestic shale production targets in China by 2020. Beijing is now in the perfect position to drive a hard bargain with Moscow, and what’s more, they refuse to touch any West Siberian gas from Russia. They don’t want to leave open any prospect that Russia will be able to use the same gas fields to supply European and Asian markets. On no account will Moscow have any arbitrage potential over China when it comes to prospective pipeline gas feeding Beijing and Brussels. The two worlds will never align for the Chinese.
That’s deeply problematic for Altai plans, precisely because all the gas would come from West Siberian fields. Russia’s grand long term plan is to pump 68bcm of gas to China, the initial 30bcm will come from pre-existing West Siberian plays, and a further 38bcm developed in its Far East. Call it chicken and egg, but China isn’t going to fall for the sucker punch. Forget West Siberia as a valid prospect; China will only sink capital into green-field East Siberian reserves sitting far closer to their border. They’ll also want heavily discounted gas prices from Russia for doing so.
Denial In Awkward Places
The sooner Gazprom understands this, the better off they’ll be. Even if China gets cheap gas, the long term volumes involved remain the only serious prize left in the global gas world. A 1% increase in Chinese gas demand equates to 25bcm consumption. It’s the one market that no gas producer worthy of the name, should let get away.
But stubborn mind-sets are of course the worst. Gazprom still thinks that oil indexation is going to hold good internationally – if they concede ground in China, it will be the thin end of the indexation wedge back in its core European market. Rather than accepting what every analyst knows, the indexation game is already up, Gazprom is not only holding firm on pricing formulas, it’s been talking up gas to liquid prospects on Eastern fields, and their old favourite threat, break-neck expansion of LNG plays feeding Asian markets. Such a shame Gazprom doesn’t actually have any serious LNG volumes to play with. Its recent $7bn LNG Vladivostok agreement with Japan merely highlighted how far Russia has to come in the liquid realm, not to mention the fact it would have been far better off sinking cash into Sakhalin II (and III) to fill Tokyo’s JCC cocktails.
But like any good patient, Gazprom has been diligent to buy ‘second opinions’ from leading Russian investment houses to reassure them they aren’t going potty. Analyst notes have been flowing thick and fast from Moscow, claiming that Chinese domestic price reforms are the nub of the problem. That and the tardy Chinese simply don’t have the necessary infrastructure to take on any serious quantities of Russian gas. Even better, the cheeky Chinese are merely holding out for swap agreements linking long term gas contracts to upstream Arctic oil concessions. It’s not like PetroChina can’t get far cheaper oil concessions elsewhere these days.
Check-up Or Check-Out
Whether you buy any of that doesn’t really matter – the bottom line is that Russia has been caught on the back foot with China. Putin misread global gas dynamics; he didn’t understand the full shale gas implications, and let Gazprom fall for its lazy assumptions that it would be able to sell expensive Siberian gas (East and West) into Asian markets. That meant playing off Japan, South Korea, India, and China in Asia, and more importantly, using it as leverage over its traditional European consumers, dictating volumes and price on a global basis.
None of that has come true. Russia is now in a serious pickle. Its new fields and old prices are all out of the money, and its supposed Asian salvation over a tired and worn out Europe, has come to naught. Whilst it’s entirely true that Moscow’s hydrocarbon links to Beijing will inexorably keep gathering pace, this is not because of Putin’s politics, but in spite of them. Gazprom has belatedly taken a small step in the right direction by asking China for capital to get Asian exports going, all they need to do now, is shift prospective fields to the East, and offer handsome discounts for Beijing’s benevolence along the way.
It’s either that, or they can keep checking into the asylum on a yearly basis. If Putin repeats the same old ‘indexed’ lines to China with nothing in return, the day might finally come when some brighter (Medvedev) chaps in Moscow have him (and Gazprom) fully committed. Then, and only then, will little old Europe have something to worry about at the other end of the Eurasian pipeline....
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b1a6580b2be0ac2bc404d29ef5a1b41e | https://www.forbes.com/sites/matthewhulbert/2012/11/26/gazprom-takes-southern-corridor-spoils/ | Gazprom Tightens Control Over European Supply | Gazprom Tightens Control Over European Supply
English: Gazprom Headquarters in Moscow
Well, it’s finally coming; Russia is starting construction of the €16bn South Stream pipeline on 7th December to make sure it retains a strong grip over South East European and Central & Eastern European gas supplies. But whether this is in Gazprom’s longer term interests remains to be seen. What’s good for ‘regional control’ is bad for Gazprom’s ‘global posture’.
Russia always had first mover advantage in the Southern Corridor purely by virtue of being able to redirect initial supplies from Ukraine towards South Stream markets. Having bought its way through corrupt SEE and CEE states, that’s exactly what it’s going to do. With final investment decisions in place, Gazprom can start offshore construction across the Black Sea - cutting through Turkish waters - before resurfacing in Bulgaria. Onshore pipes then run through Serbia, Hungary, Slovenia and into the Trans Austrian Gas Pipeline towards Northern Italy. An initial 15.75bcm will flow by 2015, ramping up to 63bcm by 2019, but let’s not beat around the bush: The moment pipeline construction starts next week, the market assumption will be that no other pipelines can compete. The EU inspired Nabucco project designed to bring Caspian and Levantine gas to European markets is ‘officially’ dead. Never to be resurrected. What’s more, Russia has just signed a 30 year supply agreement with Turkey. Gazprom isn’t just knocking out competing sources of upstream supply; it’s keeping transit states firmly under its thumb as well. ‘Russian gas, Russian prices, Russian monopoly of supply and rent’. Full stop.
The only remaining question is whether Europe might be able to squeeze some Azeri gas into Greece and Southern Italy via the Trans Adriatic Pipeline. That’s still technically possible if Gazprom decides to keep to a single South Stream tranche into Austria-Hungary, rather than splitting onshore transit in two directions (Centre and South), and if Gazprom doesn’t acquire DEPA (the main Greek utility) in an EU induced fire-sale on Greek assets. Given Gazprom’s strategic interest to make sure Azeri gas doesn’t reach European markets - and especially not at competitive spot market prices - it’s hard to see any eventuality where Moscow won’t make sure they kill off residual Azeri options in the Southern Corridor. If that’s the case, the Turks might get more Azeri gas than they originally bargained for through the TANAP pipeline, while Azerbaijan will also have to dust down LNG options, either through Turkey or Georgia as potential outlets (or a combination of both). Procrastination comes with serious costs, a valuable lesson Baku must learn for future hydrocarbon production.
Depressing stuff no doubt, but fear not, Gazprom has missed a major trick. Despite sitting on 30% of global gas supplies, Russian LNG production accounts for less than 5% of global share. Moscow has become a fringe LNG player in a globalising gas world. Gazprom never grasped the most fundamental ‘fundamental’ of all; for Moscow to remain a market maker, able to play off competing Atlantic-Pacific basin price pressures, Gazprom had to get out of pipelines and into LNG. South Stream is merely another regional nail in Gazprom’s global coffin. Rather than putting state capital where it’s most needed to get Gazprom back on track, President Putin is going for strategic ‘quick wins’.
It’s far easier building South Stream pipes to show Europe who’s boss, rather than seriously trying to sell 70bcm of gas to China, or indeed developing elephant fields to dictate terms to new gas players in the Middle East, Australasia and Africa. But until Russia gets a firmer grip on global fundamentals, it remains on the back foot. Pumping vast amounts of gas into saturated European markets via South Stream pipes isn’t just a waste of precious capital; it merely adds to overall gas market liquidity. Whatever pricing terms Gazprom thinks it’s secured, won’t mean much when excess supply makes its way onto wholesale gas hubs and prices tumble. Russia has won the Southern Corridor battle, but in doing so, stands even greater chance of losing the larger gas market war.
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697aff0dc68574e5e1ed3ab063a0814e | https://www.forbes.com/sites/matthewjcooper/2020/04/01/tiger-woods-phil-mickelson-match-to-include-brady-and-manning/ | Tiger Woods, Phil Mickelson Match Rumored To Include Brady And Manning | Tiger Woods, Phil Mickelson Match Rumored To Include Brady And Manning
Phil Mickelson and Tiger Woods will have to enforce social distancing if they conduct a repeat of ... [+] The Match. (Photo by Harry How/Getty Images for The Match) Getty Images for The Match
A repeat of 2018’s showdown between Tiger Woods and Phil Mickelson is not only reportedly set for a May date, but, in an added twist, will also include NFL legends Tom Brady and Peyton Manning.
The mooted rematch remains unconfirmed, but veteran golf journalist Robert Lusetich tweeted: “Hearing Tiger v Phil II might indeed be happening as a pay per view event but that the caveat is that each will have a partner. Two names being mentioned? Tom Brady and Peyton Manning.”
Shortly afterward, CNBC referenced “a person familiar with the negotiations”, who confirmed that AT&T’s WarnerMedia and the PGA Tour would host the event, that Mickelson and Brady would take on Woods and Manning, and that the coronavirus relief effort would benefit.
The source also suggested it would not be pay per view.
Lusetich later noted, in response to the question ‘Would this become the most gambled upon event in golf history?’: “I’d say gambling is what this is going to be about. Could be quite the rake.”
The first hints of the project were revealed on Twitter when Mickelson was asked about a replay. “Working on it,” he replied.
“Please don’t tease,” another follower pleaded. “”I don’t tease,” Mickelson responded. “I’m kinda a sure thing.”
The original head-to-head ("The Match") was promoted as both a groundbreaking exercise and also a reprise of golf’s famous challenge matches of the past.
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It was a $9 million winner-takes-all affair, with Mickelson and Woods, who were miked up, encouraged to indulge in smack talk and conduct a series of charity side bets, whilst the television coverage was advertised as revolutionary, including reporting by NBA star Charles Barkley.
Mickelson completed the victory, in dying light, on the fourth extra hole, at Shadow Creek GC in Las Vegas.
In truth, the enterprise was deemed less than a success, with the quality of the golf, smack talk and broadcast underwhelming, whilst the riches on offer to the two golfers left a sour taste in the mouth of many.
Should the rematch occur, that will, presumably, be an element of the contest which will be avoided at all cost.
However, even with a charitable aim, the exercise can expect criticism.
Sky Sports reported the news and tweeted it with the question: “Would you like to see them go head to head again?”
Steve Martin, Global CEO of M&C Saatchi Sport and Entertainment, responded: “No.”
Guardian golf correspondent Ewan Murray added: “If the last one looked crass…!” And: “I just think anything like this in the current climate would look poor. And I realise they’ll donate to charity etc but can do that anyway.”
Such views will be far from alone and a further issue may complicate plans.
On Sunday, the current social distancing guidelines in the U.S. were extended until April 30, but should those edicts be extended, by date or by precautionary measure, it could spell an end to the venture. The sport is already banned in 12 states.
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2c5a0fa04991582f58d94136de09ebd3 | https://www.forbes.com/sites/matthewkorda/2020/08/12/democrats-and-republicans-agree-phase-out-land-based-nuclear-missiles/?sh=2a6fa698109d | Democrats And Republicans Agree: Phase Out Land-Based Nuclear Missiles | Democrats And Republicans Agree: Phase Out Land-Based Nuclear Missiles
Although Democrats and Republicans increasingly seem worlds apart, when it comes to nuclear weapons issues, they’re actually much closer than one might think.
According to a new report by the Program for Public Consultation at the University of Maryland, 61 percent of Americans–including both Democratic and Republican majorities–are in favor of phasing out the United States’ aging fleet of 400 intercontinental ballistic missiles. This finding is highly noteworthy, as it runs in direct contrast to the Pentagon’s current plan of spending approximately $100 billion to buy a brand-new generation of ICBMs by 2030.
The survey, entitled “Common Ground of the American People,” is a compilation of studies conducted over the past five years, collecting data from nearly 86,000 individuals throughout the polling process. It specifically aimed to place the respondents into the shoes of a policymaker: respondents were first given an issue briefing, and were then asked to evaluate arguments for and against various policy proposals, before finally offering their recommendations.
The survey’s unique methodology is highly illuminating, because it allows readers of the report to see which arguments were deemed to be most or least convincing, and by whom. For example, Republicans preferred a proposal to phase out ICBMs while maintaining the same number of deployed warheads, while Democrats preferred a proposal to phase out ICBMs and reduce the arsenal to a lower number of deployed warheads.
The main takeaway though, is that–regardless of how the ICBM phase-out takes place–69 percent of Democrats and 53 percent of Republicans agree that the land-based leg of the nuclear triad should be eliminated entirely.
This image taken with a slow shutter speed and provided by the U.S. Air Force shows an unarmed ... [+] Minuteman III intercontinental ballistic missile test launch early Tuesday, Oct. 2, 2019, at Vandenberg Air Force Base, Calif. (Staff Sgt. J.T. Armstrong/U.S. Air Force via AP) ASSOCIATED PRESS
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It makes sense that both Democrats and Republicans would agree on phasing out ICBMs: they are outdated, destabilizing, and very expensive.
Intercontinental ballistic missiles are largely relics of the Cold War, when the United States and the Soviet Union alike feared a “bolt-from-the-blue” nuclear attack. At the time, it was believed that both countries having large land-based nuclear arsenals would prevent each other from launching a massive surprise attack. However, in today’s multipolar nuclear environment, the likelihood of such an attack is extremely slim, and so ICBMs no longer hold much strategic value. Given the abundance of more flexible options in the U.S. arsenal, U.S. Strategic Command would certainly turn to nuclear bombers or submarines–not ICBMs–in the event of a low-level nuclear crisis.
Additionally, the inherent vulnerability of the ICBM fleet actually creates a psychological pressure to launch them during a nuclear crisis, before an adversary’s missiles can wipe them out. This is why siloed ICBMs–like those deployed across the United States–are commonly referred to as “use ‘em or lose ‘em” weapons. In the event of a false alarm, accident, or miscalculation, this pressure to “use ‘em” could inadvertently trigger a nuclear war. No other nuclear weapon in the U.S. nuclear arsenal comes with this kind of destabilizing psychological pressure.
Perhaps knowing this, the Pentagon argues that ICBMs are necessary as a “hedge” in case technological advances suddenly render the United States’ nuclear-armed submarines vulnerable. However, the 2018 Nuclear Posture Review admits that “When on patrol, [ballistic missile submarines (SSBNs)] are, at present, virtually undetectable, and there are no known, near-term credible threats to the survivability of the SSBN force.” This condition is likely to continue as U.S. submarines get even quieter, thus making these fears seem relatively exaggerated.
On top of this, replacing the ICBMs with brand-new missiles would be extremely expensive. The latest estimate for the Ground-Based Strategic Deterrent, as the replacement program is called, totals approximately $100 billion. In reality, these costs are expected to rise, given that the contract will be sole-sourced to Northrop Grumman NOC after Boeing BA pulled out of the competition last year. The chairman of the House Armed Services Committee has called this development “very troubling,” and the sole-source contract has since triggered a Federal Trade Commission investigation into Boeing’s allegations that Northrop Grumman was engaging in anti-competitive behavior.
WASHINGTON, DC - JULY 9: House Armed Services Committee Chairman Rep. Adam Smith (D-WA) arrives for ... [+] a House Armed Services Committee hearing on July 9, 2020 in Washington, DC. At an event in October 2019, Smith noted that awarding a sole-source contract for the ICBM replacement program was "very troubling." (Photo by Greg Nash-Pool/Getty Images) Getty Images
Given these underlying programmatic and strategic concerns–in addition to the new survey demonstrating that both Democrats and Republicans want to phase out ICBMs entirely–why is this $100 billion project still moving forward? In the midst of an election, a recession, and a devastating pandemic, it seems like common sense to delay the program at the very least.
However, a robust lobbying effort by weapons contractors has impeded public scrutiny of the program. Northrop Grumman–the only bidder for the ICBM replacement contract–spent more than $162 million on lobbying between 2008 and 2018, with the bulk of the contributions going to members of the “ICBM Caucus”–a coalition of Senators from states where ICBMs are deployed. In 2018, this lobbying effort helped kill an amendment to the National Defense Authorization Act which called for a feasibility study on extending the life of the current ICBM force, rather than rebuilding it from scratch. This has had the effect of suppressing public debate over the future of the ICBMs; without studies like this one, the public is being asked to blindly swallow the pro-ICBM claims of those that would materially benefit from their replacement.
The University of Maryland's report offers a new tool to push back against the “business” of nuclear policy. The survey suggests that corporate lobbying and “special interests” are alienating the public from their elected representatives, and dividing the two political parties even further. Therefore, treating its respondents as neutral “policymakers” clearly demonstrates that without the presence of moneyed interests, Democrats and Republicans agree on much more than one might think. And in this particular instance it is clear: majorities from both parties want to phase out intercontinental ballistic missiles.
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425f0855e3db5a8cfd8744af9da53bdc | https://www.forbes.com/sites/matthewnewton/2011/09/30/resurrecting-the-deleted-city-of-the-internets-early-pioneers/ | Resurrecting 'The Deleted City' Of The Internet's Early Pioneers | Resurrecting 'The Deleted City' Of The Internet's Early Pioneers
When the Internet was young, before Blogger, WordPress, and Movable Type enabled the public to easily publish volumes of information to the world, sites like GeoCities provided a free home. Like so many services that were free in the early days of the Internet, annoyances such as endless pop-up ads and poor design were often unavoidable. But even with the small space that GeoCities provided a user, some ambitious pages were built.
For a new project titled "The Deleted City" (see above), GeoCities has been visualized as a massive city with street-like grids and exploded views. It's an interesting way to look back at the early days of digital culture, those that preceded social media. Background on The Deleted City:
The Deleted City is a digital archaeology of the world wide web as it exploded into the 21st century. At that time the web was often described as an enormous digital library that you could visit or contribute to by building a homepage. The early citizens of the net (or netizens) took their netizenship serious, and built homepages about themselves and subjects they were experts in. These pioneers found their brave new world at Geocities, a free webhosting provider that was modeled after a city and where you could get a free "piece of land" to build your digital home in a certain neighbourhood based on the subject of your homepage. Heartland was – as a neigbourhood for all things rural – by far the largest, but there were neighbourhoods for fashion, arts and far east related topics to name just a few. Around the turn of the century, Geocities had tens of millions of "homesteaders" as the digital tenants were called and was bought by Yahoo! for three and a half billion dollars. Ten years later in 2009, as other metaphors of the internet (such as the social network) had taken over, and the homesteaders had left their properties vacant after migrating to Facebook, Geocities was shutdown and deleted. In an heroic effort to preserve 10 years of collaborative work by 35 million people, the Archive Team made a backup of the site just before it shut down. The resulting 650 Gigabyte bittorrent file is the digital Pompeii that is the subject of an interactive excavation that allows you to wander through an episode of recent online history.
After watching the video (above), or visiting the project site, it's hard to know if or when the 650 gigabyte GeoCities file will be made available to the public. But maybe projects like this mark the next phase of Internet fanaticism: Digital archeology.
Email me. Follow me on Twitter. Visit my personal blog.
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356892951a04648e10c0edf401c62572 | https://www.forbes.com/sites/matthewstepp/2013/01/02/the-past-present-and-new-year-of-u-s-clean-energy-policy/ | The Past, Present, and New Year of U.S. Clean Energy Policy | The Past, Present, and New Year of U.S. Clean Energy Policy
When President Barack Obama was inaugurated on January 20, 2009, clean energy was largely a policymaking afterthought. Federal investment in clean energy research and development (R&D) stood at just over $4 billion a year - less than 40 percent of its peak in the 1970’s. Policy support for clean tech commercialization, demonstration, and deployment was in equally bad shape, plagued by boom-and-bust periods of expiring incentives and on-again, off-again subsidy extensions. “Innovation” was little more than a political buzzword in the energy policy debate. Making matters worse, economic collapse cast doubt on the prospect that existing levels of funding for clean energy would even be maintained, and that the nascent clean energy industry could survive.
It’s an understatement to say a lot has changed in the four years since. As we flip the calendar to 2013, it’s important to take a moment and take stock of where clean energy policy has come in the last four years and what challenges it faces today to inform what needs to be done in the next four years (and beyond).
U.S. Clean Energy Policy Under the First Obama Administration (2009-2012)
There can be no doubt that the first Obama administration implemented several important energy policy initiatives. For example, the past four years have seen the following highlights:
Historic public investment in the energy sector: Aided in large part by the American Recovery and Reinvestment Act of 2009, the federal government is expected to invest more than $150 billion on clean energy R&D, demonstration, and deployment between 2009 and 2014 – more than three times what was spent in 2002-2008. Specifically, as previously noted on this blog, TIME Senior National Correspondent Michael Grunwald observes that Stimulus funds “revived the wind industry and the rest of the clean-tech sector from a near death experience” and “has financed the world’s largest wind farm, a half-dozen of the world’s largest solar farms, the nation’s first refineries for advanced biofuels, a new battery industry for electric vehicles, unprecedented investments in cleaner coal and a smarter electric grid and over 15,000 additional clean-energy projects.” Full funding for the Advanced Research Projects Agency-Energy (ARPA-E): As ITIF has noted, ARPA-E is now “a leading force for energy innovation in the country, if not the leading force.” But it wasn’t always so. ARPA-E – the United States lead program for investing in high-risk, high-reward energy technologies the private sector is unwilling or unable to support - was authorized during President George W. Bush’s administration but didn’t receive appropriations until the Obama administration. Although just barely three years old, the agency has provided $521.7 million in grants to more than 180 projects located in 34 states, across 12 very diverse program areas. The agency has also helped encourage private investment – 11 of the projects funded by ARPA-E to the tune of $40 million have leveraged more than $200 million in follow-up private funding (All as of May 2012) due to successfully meeting research goals.” Beginning to roadmap public investments in clean energy: The Department of Energy released its inaugural Quadrennial Technology Review, which comprehensively assessed the DOE’s energy technology R&D programs, National Lab research and clean energy technological progress to inform better department R&D strategies moving forward. Building collaborative energy R&D projects: DOE established several Energy Innovation Hubs across the country aimed at solving complex, multidisciplinary research problems related to next-generation energy technologies by bringing together the best researchers from the National Labs, Universities, and Industry. These Hubs aim to solve leading technology problems related to solar energy, energy efficiency, and nuclear energy. The creation of the fourth Hub, focused on battery and energy storage technology development, was announced in late November 2012. Making manufacturing an energy innovation policy priority: The Obama Administration implemented or is implementing a series of promising manufacturing policy initiatives, like the establishment of the Advanced Energy Credit for Manufacturers (which has sun-setted) and the National Network for Manufacturing Innovation. The NNMI is particularly important as it sets to create up to 15 hubs of manufacturing innovation around the country to work on cross-cutting technology issues related to making American energy manufacturers competitive. As I have pointed out on this blog, a failure to adequately support clean energy manufacturing is a warning sign that the United States is losing the global clean energy race.
U.S. Clean Energy Policy Under the Second Obama Administration (2013-2016)
Nevertheless, for all the first Obama administration’s energy policy accomplishments, much more work remains to be done to strengthen and streamline the national clean energy innovation ecosystem. It will continue to be a challenge to halt and reverse declining public investments in clean energy and counter the effect of annually expiring deployment incentives. Furthermore, political gridlock at the federal level will make it tough to accomplish broad reform. But that does not mean policymakers should not strive for good policy. As such, as we move from commenting on the past four years to looking to the next four years, President Obama’s policy agenda should include:
Appointing a reform-minded Energy Secretary: As I wrote last month, as Secretary Steven Chu is expected to leave the Energy Department, the president needs to pick an able replacement, with “a clear understanding of the innovation process and an eye towards continuing reforming the DOE. Recommendations include former ARPA-E Director Arun Majumdar, exiting MIT President Susan Hockfield, and former Lockheed Martin Chairman Norman Augustine. Increasing public investment in clean energy RD&D: According to ITIF’s Energy Innovation Tracker, the federal government currently invests roughly $6 billion per year in clean energy innovation programs. Yet in comparison to other leading innovation challenges, clean energy is significantly underfunded: the United States annually invests $9.5 billion for space exploration, $30 billion in healthcare research, and $70 billion to develop new weapons. Leading energy experts and thinkers have called for ramping up public investments to $15-25 billion per year to spur the development and deployment of cheap clean energy technologies. The administration should double clean energy innovation investment to at least $15 billion per year. Reforming public research institutions to better support clean energy technology commercialization: The President and policymakers should aim to refocus DOE's mission to explicitly include energy innovation. As previously laid out, this requires taking a look at reforming the DOE itself by eliminating Department-wide energy innovation micromanagement and strengthening the National Labs system. One way of doing this is to reform the mission of the National Laboratory system so that barriers to the labs partnering with industry are removed and that labs are rewarded in part on the basis on research outcomes and performance and not just outputs like number of patents. The Labs should be provided more flexibility to invest in energy research ideas, build collaborations, and manage its research infrastructure. Additional steps should be taken to officially link key DOE innovation programs with DOD’s operational energy strategy so that DOD’s procurement system can leverage DOE’s RD&D investments, providing both benefits to the military as well as support the scale-up of new energy technologies. Establishing a dedicated revenue stream for clean energy innovation programs. The boom-and-bust cycle of federal funding for clean energy had contributed to substantial policy uncertainty for the industry, with hampers long-term planning efforts. Furthermore, fiscal austerity threatens funding for clean energy in general; establishing a dedicated revenue stream, akin to federal gas taxes going to the Highway Trust Fund and thus funding transportation infrastructure, would overcome these issues. In that vein, options for a dedicated clean energy innovation revenue stream include royalties from energy production, a carbon tax, and ending fossil fuel subsidies and redirecting those funds. Establish “smart” clean energy deployment policies: The clean energy subsidy debate is one of the most contested, but unsophisticated policy debates in Washington today. It largely boils down to a specific energy industry fighting to extend its preferred subsidy and anti-clean energy advocates fighting to eliminate said subsidy. As a result, little attention is paid to how these policy incentives impact clean energy innovation and whether energy technologies need different types of support or better deployment support all together. Reforming clean energy deployment policies so they become active tools in driving down costs, increasing performance, and supporting emerging technologies is crucial for connecting the public investments in energy R&D to market and moving clean energy from niche product to industry leader.
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4c5a3e23b55ce7c4e4916aef1d9c706c | https://www.forbes.com/sites/matthewstibbe/2011/05/19/deadhead-flights/ | How to fly Private Jets at Airline Prices | How to fly Private Jets at Airline Prices
Image via Wikipedia
For the first class crowd, a private jet is the ultimate upgrade. But buying or chartering is too expensive for all but a few. So how do you get to fly on a business jet for business-class prices?
Fly empty sectors
The first option is to buy a seat on a 'deadhead' positioning flight. After a chartered plane has delivered its VIPs to their destination it has to fly empty back to base or onto its next pick-up point. Some charter companies offer seats on these flights at surprisingly low prices.
Around 40 percent of all private jet flights operate empty so there are rich pickings if you're savvy about it.
Of course, you lose the flexibility of picking the time and route but you get all the other amenities like private terminals, comfortable seats and the 'master of the universe' feeling.
Check out AirPartner's Empty Sector site. (They have a royal warrant to fly the Queen so you could be sitting in her seat one day.) They have flights from Van Nuys to Nice, France, Amsterdam to Kieve as well as shorter European hops for up to 75% off. A quick online search for 'empty leg' or 'deadhead flights' will reveal many other providers.
My own experience of this was exciting and disappointing in equal measure. My wife and I took a deadhead flight from Biggin Hill to the South of France a few years ago. The plan was to fly to Nice, which is where we booked our hotel but at the last minute, the plane had to go to Genoa and so we had to take a two-hour trip on a grotty Italian train to get to our final destination. It was like a glamorous night out that ends in the gutter. But for a few hundred pounds, the adventure was worth every penny. (But I prefer to fly myself when I can.)
Resurrect DayJet
A second option disappeared in 2008, when DayJet stopped trading. They were using Eclipse 500 very light jets to fly from smaller airports in Florida. They promised 'pay-per-seat, on-demand' travel. Members could request a flight from point a to point b and they would get confirmation and a price. However, if other members bought empty seats on that flight, the cost would go down. A clever booking system orchestrated the schedule, prices and availability. It's a good idea. James Fallows wrote a great article about it in The Atlantic. The technology lives on and perhaps this business model will reappear.
Social flights
What happens if you combine Groupon or Facebook with jet charter? You get Social Flights. Organise a group of friends or join an existing group to book a private jet at a lower price. Or at least, that's the theory. Fast Company wrote about them recently. The site today listed 22 flights with seats starting at $150 each. If they get enough trips and enough members to make it viable, it could be a great way to experience private aviation.
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877b6a40e806d18578de9cbd0d42e0c3 | https://www.forbes.com/sites/matthewstibbe/2013/05/06/googles-shiny-new-82-million-airport-terminal-in-silicon-valley/ | Google's Shiny New $82 Million Airport Terminal In Silicon Valley | Google's Shiny New $82 Million Airport Terminal In Silicon Valley
Interior rendering for Google's new FBO in Silicon Valley. Source: San José International Airport
A few years ago I taxied past a hangar at San Carlos airport. The door was open to the immaculate interior and I could see an array of jets and aerobatic light aircraft. My instructor said it was Larry Ellison’s private plane collection. Not for nothing is the airport known to IATA as SQL, after Oracle ’s database language. From my little Diamond Katana, I looked on in envy.
Now Google executives are putting Oracle in the shade, at least when it comes to impressive aviation facilities. According to TechCrunch, Larry Page, Sergey Brin and Eric Schmidt have eight private jets between them. Including a converted 767 dubbed the ‘party plane’.
Airside artist's mockup showing private jets outside the new terminal. Source: San José... [+] International Airport
Now they have gone into partnership with Signature Flight Support to build an $82 million fixed base operation at San José International Airport, including an executive terminal, seven hangars (five for Google, apparently), ramp space for converted airliners and servicing facilities.
Beats fighting the crowds at the regular terminal - pull up at the new FBO. Source: San José... [+] International Airport
The project will generate around 150-200 construction jobs and 36 permanent on-airport jobs plus hundreds more off-airport. But for Google executives and other Silicon Valley bigwigs, it’ll be an elegant and efficient way to start their journeys.
(Hat tip: The Verge)
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Gallery: Topflight Airport Lounges 12 images View gallery
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f191f00d2bfd2fffaa98eb06715fad03 | https://www.forbes.com/sites/matthickey/2013/09/12/hbos-cto-unattached-hbogo-is-a-no-go/ | HBO's CTO: Unattached HBOGo Is A No-Go | HBO's CTO: Unattached HBOGo Is A No-Go
SAN DIEGO, CA - JULY 19: Game of Thrones writers and cast members, still available only via cable,... [+] satellite, or piracy. (Image credit: Getty Images via @daylife) The big question is: will @hbogo be able to handle tonight’s traffic? Early signs point to no. #got... [+] (Photo credit: irish-girl)
Many of us are still holding our breath for a way to watch HBO’s original programming without a cable subscription, but it seems as if we’re all about to turn collectively blue in the face.
Speaking at the GeekWire Summit in Seattle today, HBO’s CTO Otto Berkes said that HBO has “an extremely powerful and effective business model. It would not make sense to disrupt that unless the upside were significantly higher than any potential downside.” So that, it would appear, is that, to the dismay of the many who want to consume HBO programming but don't want to fork over money for other channels they don't really want.
Berkes noted, though, that HBOGo was quite successful and that 60% of HBOGo users were using mobile devices to view content. He didn’t comment on the percentage that use devices like the Apple TV, nor could he confirm that HBOGo would be coming to the Xbox One. He did say, though, that HBO was interested in being on all the most “popular platforms going forward”, which both the Xbox One and PS4 would likely qualify as, one would wager.
He also mentioned that the recently opened engineering office here in Seattle is “a real cornerstone for our future plans. We are hiring hardcore software developers who could potentially do anything.” Indeed, a quick search finds a couple of intriguing open positions for those devs.
The GeekWire Summit goes throughout the day and you can watch it here.
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a19f6d09877dd055f65380f5fa95a409 | https://www.forbes.com/sites/matthickey/2014/04/11/amazons-comixology-acquisition-has-some-readers-concerned/ | Amazon's ComiXology Acquisition Has Some Readers Concerned | Amazon's ComiXology Acquisition Has Some Readers Concerned
Amazon yesterday announced that it would be acquiring ComiXology, a combo app and store for comic books on digital devices. Think of it as an iTunes for the Marvel and DC crowd.
The app is quite popular with tablet owners that consume comics. Anyone who’s ever read a comic knows that they’re typically formatted with several panels per page, and the ComiXology app uses a patented technology called Guided View that lets users follow the action one panel at a time, making for a very linear and elegant way to present a story.
In addition, ComiXology’s store offers most mainstream titles at the same time that they hit physical store shelves, usually at the same price.
But the part that Amazon is likely most interested in is ComiXology’s self-publishing platform, that allows independent authors and artists an avenue to get their comics in the hands of fans while making a bit of money at the same time.
According to David Steinberger, ComiXology’s CEO, the brand would remain as it is as a subsidiary of Amazon. This is good news to digital comics fans, as for many, the app’s ecosystem has completely replaced the purchase of paper comics. But some questions remain for readers.
“I worry about where that leaves digital partners,” says Jason Lamb, a Seattle-based digital comics expert. “There’s a program that lets local stores sell ComiXology digital comics [and they receive] a small percentage. That was a really great gesture from ComiXology, they being retail’s direct competitors. I think that's out of a love for all things comics on their part.”
I asked if he thought it was likely Amazon would keep that program going, and Lamb told me, “I don't see Amazon being so kind regarding that initiative. In the recent past, Amazon had a deal with DC so that it could sell their collections through the Kindle store exclusively. I would think that had something to do with the physical distribution side, as it doesn't make practical sense when ComiXology has far more readers, exposure, and cross pollination of brands.”
There’s also concern that Amazon may hinder further development on non-Kindle tablets, like the Apple ’s iPad. That seems unlikely, though, as Amazon has been pro-active on making apps for other platforms. It’s quite easy to read Kindle books on a Samsung Galaxy Tab, for example.
Still, Amazon isn’t being very forthcoming with information about the acquisition. “I hope they'll invest in better reading experiences, such as higher resolution scans, or a better user flow,” Lamb said. A spokesperson refused to comment on Amazon’s plans by the time this story went live, and Amazon’s silence is making some fans nervous. “That makes me suspicious about this acquisition.”
ComiXology booth! (Photo credit: PatLoika)
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7cb6c5143a7572a404c354bacab93a38 | https://www.forbes.com/sites/matthickey/2015/09/26/if-netflix-is-indeed-insourcing-tv-production-then-it-may-change-tv-forever/ | If Netflix Is Indeed Insourcing TV Production Then It May Change TV Forever | If Netflix Is Indeed Insourcing TV Production Then It May Change TV Forever
Apparently not content with using the traditional broadcast model of acquiring television shows for broadcast, Netflix is said to be doubling down into the business of producing its own shows in-house. And if the report from Bloomberg Business is to believed, Chelsea Handler’s new show might be the first to make it to the public.
Generaly speaking, most networks don’t produce their own shows but rather broadcast shows made by other production companies. Mythbusters, for example, is broadcast on Discovery but is written, shot, and produced by Australia’s Beyond Television Productions. Netflix has been following this same model of taking shows from outside studios and paying for the rights to be the sole broadcaster. And so far it’s worked out quite well – subscriptions are up and the network has garnered nearly a dozen Emmys, the first streaming network ever do so.
The Netflix Inc. website displays the and quot;Orange is the New Black and quot; and and quot;House... [+] of Cards and quot; series on laptop computers in this arranged photograph in Washington, D.C., U.S., on Thursday, July 10, 2014. and quot;House of Cards, and quot; and and quot;Orange Is the New Black, and quot; two Netflix Inc. series that have boosted the popularity of online viewing, will compete for television's top honors as nominees for Emmy awards in drama and comedy. Photographer: Andrew Harrer/Bloomberg
The original content – marketed under the creative name of “Netflix Originals” – is broadcast on Netflix alone, but the deals to do so are often limited by time. When, say, the seventh season of Marvel’s Daredevil comes around, Disney might be eligible to shop around for a better distribution deal. If that happens then Netflix could find itself losing its subscribers due to losing its content.
The advantage of producing its own shows is that Netflix can own them perpetually; the disadvantage, though, is that it also takes on all of the financial and operational risks, which can be substantial.
Those are the main reasons why traditional networks don’t use a self-production system, but then Netflix isn’t a traditional network in any way – as of five years ago it barely existed as anything more than a Blockbuster-killing film delivery vehicle – and the fact that it’s entirely based on new technology instead of being restricted by infrastructures of the past means that it doesn’t have to do things the old way. In fact, it’s built specifically to do the opposite.
While one can’t expect the Foxes, NBCs, or AMCs of the world to follow suit, one can also expect the Hulus and Amazons to do just that. The wild card here, of course, is Apple , with the rumors of Apple entering the original TV market just as it did the music market just not going away. In fact, they’ve only gotten louder since it announced its next-generation Apple TV a couple of weeks ago.
If it comes to the execution phase, an in-house studio for Netflix won’t just disrupt the world of broadcast television but also the world of television production. It’s likely that established studios are keeping an eye on the move, as if it’s more than moderately successful it could seriously affect how they do business, for better or worse.
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c472d814c38f0ea79e1b382f89d09521 | https://www.forbes.com/sites/matthickey/2015/10/31/facebook-testing-craigslist-threatening-marketplace-for-selling-to-online-friends/ | Facebook Testing Craigslist-Threatening Marketplace For Selling To Online Friends | Facebook Testing Craigslist-Threatening Marketplace For Selling To Online Friends
I’m cheap. Like, really cheap. I’m a journalist, we're supposed to be like that. Thus I do a lot of my shopping online, but Amazon doesn’t get all of my money. No, sometimes I like to keep it local, and I’ve had some great success finding things I want-and-or-need on Craigslist. But Craigslist has its problems – you don’t know your buyer or seller, it can be hard to organize a sale or pick-up, and, well, it can be downright sketchy. One thing that would help would be a referral or ranking system, yet Craigslist has nothing of the type – once a deal is done then it’s done, no ratings or feedback involved.
Facebook , it seems, is again working on a competitor to fill that void as well as others. It’s had the idea for a while; way back in the Bush administration it had a “marketplace” section but it never really took off. And just a couple of years ago I personally saw a prototype of a new marketplace that was meant to usurp Craigslist but it was apparently placed on the rhetorical back burner.
Now, though, reports are circulating that Facebook has figured out its marketplace and if it’s anything like the one I saw back when I had less of a waistline and the revamped version could be a winner. Facebook has confirmed that it is, indeed, testing just such a system.
TechCrunch has it that Facebook is testing a classified ads feature in a few small local markets, which itself isn’t at all out of the ordinary. But what it does could change how we buy and sell used goods (among other things) due to Facebook’s inherent social features.
One possible scenario that I was shown was that of a hypothetical person selling a TV (again, this was two years ago, but I’d be amazed if it didn’t work in a similar fashion). This person would post an “ad” (for lack of a better word at this point) stating that they had a TV of certain stats available for a certain price. Similar posts already happen regularly on Facebook, and there are local groups in many communities just for the buying and selling of used goods. These posts generally include something along the lines of “please tell your friends!” The Facebook app, though, would essentially do just that.
Let’s imagine a person in the area -- it would generally be location-based for obvious reasons -- posts that they’re looking to buy a TV. If that person has a close connection on the social network to person above selling a TV – say a friend of a friend, or a friend’s friend’s friend – then they might see their ad as a suggestion, along with whom they may know in common. This way, the buyer can get information about the seller from the mutual acquaintance as a way to minimize personal risk.
In other words, Facebook would play matchmaker between a potential buyer and a motivated seller via social connections that already exist. "Your friend Jill knows someone looking to sell a 40-inch plasma TV, click here to learn more!"
A simpler scenario would be that person looking for a TV simply going to the marketplace section and clicking on something along the lines of “see who’s selling TVs near me”. They'd get the all the local sellers as they're connected to them and would be prompted to reach out. Any of these scenarios means that the marketplace would work to reduce the sketchiness aspect of shopping for used items online and would also help sellers get their goods in front of the eyeballs by those who are specifically interested.
It’s a win for both sides, but could be a serious threat to Craigslist.
Facebook will perhaps insist that any monetary transactions happen via its own payment platform, and it would likely take a small fee. But considering that it could automate the selling and discovery of personal sales it might be a welcome addition to the marketplace.
For its part, Facebook has confirmed to TechCrunch that it has a local marketplace application being tested in the wild now, however it refused to divulge any other real information. Still, it’s a feature that isn’t surprising for the website that’s striving to be the be-all and end-all of the Internet. If it can pull it off then I personally know where I’m buying my next barbecue – I don’t want to get one of those from someone named Wayne that I just met from Tacoma.
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947be34aa6642f48b612017167e22387 | https://www.forbes.com/sites/matthickey/2016/05/17/with-an-80-million-budget-the-tetris-movie-youve-been-waiting-for-is-on-the-way/ | With An $80 Million Budget, The 'Tetris' Movie You've Been Waiting For Is On The Way | With An $80 Million Budget, The 'Tetris' Movie You've Been Waiting For Is On The Way
We’re not sure why, but a combined Chinese and American production studio has pressed start on a feature film based on the best-selling video game series Tetris.
Yes, the Russian Tetris, with the memorable music and falling blocks that was launched to worldwide fame when it was packaged with Nintendo’s GameBoy handheld gaming systems in the 80s. The one where one would wait endlessly for the four-brick long piece to fall so that they could score the game's namesake. That Tetris.
The film has an $80 million budget and will be produced by Threshold Global Studios, a partnership between America-based Threshold Entertainment Group and China’s Seven Star Works. The producers, Bruno Wu and Larry Kasanoff, envision it as an “epic sci-fi thriller” -- and also as the first installment of a trilogy, of all things.
A visitor plays the video game Tetris (1984) during an exhibition preview featuring 14 video games... [+] acquired by The Museum of Modern Art (MoMA) in New York, March 1, 2013. The MoMA acquired 14 video games entering its collection as part of an ongoing research on interaction design. AFP PHOTO/EMMANUEL DUNAND (Photo credit should read EMMANUEL DUNAND/AFP/Getty Images)
The news comes just before of the release of two other films based on best-selling video games: The Angry Birds Movie and Warcraft. While it’s easy for the average person to discern what these films are about, it’s not so easy with Tetris. Kasanoff told Deadline that Tetris would be “not at all what you think; it will be a cool surprise.” Which is refreshing, because we have no idea how to even start thinking about a Tetris movie.
To be fair, Kasanoff has credits that include co-founding Lightstorm Entertainment with James Cameron, and produced action-thriller True Lies as well as the epic sci-fi film adaption of the video game Mortal Kombat, both of which were massive hits and quite enjoyable.
So maybe The Tetris Movie can become a hit and achieve a box office high score. We’ll be watching this one, because no matter how the bricks fall it’s bound to be a doozy.
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ef020248a4891bd1da10675edeb7168a | https://www.forbes.com/sites/matthougan/2018/05/23/what-golds-history-teaches-us-about-bitcoin-as-a-store-of-value/ | What Gold's History Teaches Us About Bitcoin As A Store Of Value | What Gold's History Teaches Us About Bitcoin As A Store Of Value
Shutterstock
The most compelling use case for Bitcoin today is as a store of value. But too often, people dismiss the idea because of Bitcoin’s volatility.
How can it be a store of value when its price moves 20% in a month?
It’s a refrain we’ve heard recently from J.P. Morgan, Goldman Sachs and Vanguard, among others. Typically, these people compare Bitcoin to gold and decide it falls short.
Gold is solid. Bitcoin is volatile. It’ll never work.
These statements are ignorant of gold’s history and devoid of imagination.
What the History of Gold Teaches Us
The 1970s are a dividing line for gold. Before 1971, the U.S. dollar was hard-backed by gold, and gold’s value was effectively vouchsafed by the full faith and credit of our government.
When Richard Nixon took the U.S. off of the gold standard in 1971, it set gold loose from its moorings. What followed was a period of huge volatility, as gold fought to establish itself as an independent store of wealth. In 1974, for instance, gold bullion prices rose 73%, before falling 24% in 1975. In 1981, gold lost 33% of its value, after being up 121% just two years prior.
Gold Prices Post Gold Standard Year Return Year Return 1972 43.14% 1977 20.43% 1973 66.79% 1978 29.17% 1974 72.59% 1979 120.57% 1975 -24.20% 1980 29.61% 1976 -3.96% 1981 -32.76% Source: Opengold.
You can almost hear the naysayers now: How can you call it a store of value when it loses one-third of its value in a single year?
What a New Store of Value Looks Like
This volatility is what you’d expect from a new store of value. Insisting that a new store of value emerge fully formed in its long-term steady state is asking too much. In fact, you would expect two things from any store of value as it established itself:
A Rapidly Appreciating Price At First, Slowing Over Time: The price of a new store of value would likely start out very low, as few would believe in it. As it became established, prices would rise exponentially. Over time, this price appreciation would slow as it reached a steady state. High-But-Declining Volatility: Similarly, early volatility would be extreme, as its long-term sustainability would be in question. But over time, that volatility would tail off as the asset became more established.
That’s exactly what we saw in gold, and Bitcoin is following the same path. Bitcoin’s price rose exponentially in its earliest days, and that growth is slowing over time. Volatility—while still high—has declined markedly, and will likely fall further as derivatives and market-making activity increase.
Bitcoin Volatility Is Declining Over Time Buy Bitcoin Worldwide
Why Store of Value Matters: The Valuation Case for Bitcoin
The store-of-value argument is important because it answers the biggest question surrounding Bitcoin: What is it worth?
A store of value is worth what people will pay for it. While gold has some use as an industrial metal and in jewelry, it would not trade for $1,300 per ounce based on those uses alone. It’s worth $1,300 per ounce because people are willing to pay $1300 per ounce for it as a store of wealth.
If you accept Bitcoin as an emerging store of value, you can look at the current price and argue it’s cheap. The current market cap of Bitcoin—the value of all Bitcoin in existence—is $143 billion. The current market cap of gold is somewhere around $7.5 trillion. In other words, Bitcoin is storing around 2% of the wealth of gold.
Look out 10 years: As the digital world becomes an ever-larger part of our lives, and the millennial generation moves into its prime age range for saving, it’s not hard to imagine a world where Bitcoin holds 1/10th the value of gold. That would imply a 500% price increase, from current levels of around $8,000 to about $40,000.
Could Bitcoin’s value be equal to gold? That would suggest a shade under $400,000.
Could it be higher, because Bitcoin has more potential utility?
Don’t listen to the folks who say Bitcoin will never be a store of value. It’s actually right on track, following in the footsteps of every other significant store of value that’s come into the world. There’s no guarantee it will stay on that path, but if it does, the opportunities are significant.
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7e69b9a13110598bd3cdc68ab21bc803 | https://www.forbes.com/sites/matthougan/2019/08/21/bitcoin-vs-gold-is-bitcoin-really-a-new-safe-haven-asset/ | Bitcoin vs. Gold: Is Bitcoin Really A New 'Safe Haven' Asset? | Bitcoin vs. Gold: Is Bitcoin Really A New 'Safe Haven' Asset?
Is bitcoin a new digital gold?
That’s the question on everyone’s mind recently.
Is bitcoin the new gold? Yes ... but it's gold circa 1973. (Photo by Ulrich Baumgarten via Getty ... [+] Images) U. Baumgarten via Getty Images
Over the weekend, Barron’s laid out the skeptical case in an article titled “Is Bitcoin A Safe Haven?”:
“This week certainly would appear to qualify as a good test for an asset’s safe-haven bona fides,” the magazine wrote. “There was a market meltdown in Argentina, escalating trade tensions between the U.S. and China, inversion of the Treasury yield curve (viewed as a recession indicator), grim economic news from Germany, and anti-government protests in Hong Kong.”
And yet, it noted, bitcoin ended the week down 10%.
I guess the whole “bitcoin = digital gold” thesis is dead, right?
Wrong.
Bitcoin Is Like Gold … Just In The 1970s
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Safe haven assets are supposed to be boring. Take gold, for instance: The annualized return of gold since 1980 is 2.3%/year. Adjusted for inflation, it’s -0.7%/year. While there have been good years, like the 2000s, for the most part, it’s just sat there, like a dumb rock, holding its value.
Which is, after all, what it’s supposed to do.
If you’re interested in wealth creation, history suggests you don’t actually want a store of value; you want an emerging store of value. That is, an asset that has all the characteristics of a store of value, but doesn’t yet have widespread acceptance amongst investors.
We know this by studying the history of gold. The vast majority of returns gold has enjoyed in the modern era came in the 1970s. Consider the returns by decade:
1970s: 1,365% 1980s: -22% 1990s: -28% 2000s: 281% 2010s: 50%
The 1970s was, of course, when the U.S. abandoned the gold standard. At the time, people didn’t know what to make of gold. Would it succeed as a “safe haven” asset, untethered from the dollar, or be cast aside as a “barbarous relic,” as John Maynard Keynes once called it?
The result was a period of significant volatility, as the two forces argued back and forth. There were years, like 1975, when gold tumbled in value, falling 25%. And years, like 1979, when it soared, rising 120%.
There was daily volatility too: In 1973, gold’s price moved more than 3% one out of every ten days! Sounds almost like bitcoin to me.
It was exactly this risk, however–the possibility that gold could be cast into the dustbin of history, like cowry shells and other forgotten stores of value–that led to gold’s volatility and strong returns. As evidence mounted that gold would in fact continue to serve as a safe haven, returns spiked and more investors made gold a part of their portfolios.
That same process is taking place in bitcoin today.
(Note: In the mid-2000s, gold saw a large run largely catalyzed in part by the launch of the first gold bullion ETF, the SPDR Gold Shares (GLD), which opened up access for a new wave of investors; easy monetary policies also helped).
Bitcoin Is Both A Safe Haven Asset And Volatile. Let’s Get Used To It.
People love to make analogies and put unfamiliar things in a box. The bitcoin=gold narrative is an easy crutch because bitcoin shares many characteristics with gold. It’s scarce, portable, fungible, divisible, doesn’t degrade over time, and has value even though it has no cash flows. Moreover, in certain moments, bitcoin has shown signs of behaving like a classic store of value. When the U.S. labeled China a currency manipulator in early August, for instance, bitcoin prices spiked.
But at the same time, bitcoin is also a risk asset. It’s new, and much like gold in its first decade, its long-term position in the world is not yet secure. As a result, it shares characteristics with other risk assets, like stocks and venture capital investments. When markets enter a risk-off mode, some buy it as a safe haven while others lose faith and sell to peel back their risk.
These two forces—shelter from macro threats, and exposure to risk—can come into direct conflict. When the market stumbles for macro reasons, for instance, the day-to-day returns of bitcoin become hard to parse.
Over time, however, the dominant paradigm is clear: Bitcoin is an “emerging store of value.” Each day, more investors gain greater confidence in bitcoin’s place in the world. Each day, it gets easier for institutional investors and financial advisors to buy. Each day, millennials—who prefer bitcoin to gold by a 9-to-1 ratio—inch closer to their prime investing years.
Like gold in the 1970s, this has translated into volatile but strong returns. Given the level of skepticism that remains about bitcoin’s role in society, there’s still plenty of upside left.
Some day, maybe, bitcoin will also be boring as dirt. But chances are, if we get to that point, prices will be significantly higher than they are today.
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44c213ee4013e1cc739a309ca0ecd28d | https://www.forbes.com/sites/matthunckler/2015/05/08/collaboration-fuels-startup-community-in-north-carolinas-triangle/ | Collaboration Fuels Startup Community in North Carolina's Triangle | Collaboration Fuels Startup Community in North Carolina's Triangle
"The Triangle startup scene is rock n’ rolling," effused Steve Case, the AOL co-founder and renowned tech investor. "People are working together to help each other, help each company be successful, and help the area grow as a startup region."
On May 5th, Case’s Rise Of the Rest Tour stopped in the northeastern North Carolina area, which includes Raleigh, Durham, and Chapel Hill. This is his third road trip in the past year with the goal of highlighting hotbeds of entrepreneurship outside of Silicon Valley and New York.
"We’re trying to shine a spotlight on the regions that are up and coming," Case explained. “In some ways, the Triangle has already risen.”
You can watch the recap here:
Not only do several established tech giants, including Cisco and IBM , have hubs in the area, but newer companies are turning heads with valuable IPOs. Durham has seen six companies acquired in just the last 24 months for a total of over $1 billion.
For the smaller startups, the Triangle has many amenities that have helped it become such a startup boomtown: a high-tech research and development center in the Research Triangle Park, talent from research universities like UNC and Duke, a startup support organization called CED, coworking spaces, and several accelerators.
In fact, after analyzing 11 key metrics, financial research firm WalletHub ranked Raleigh second in its recent "Best Cities to Work for a Small Business" list.
Case toured HQ Raleigh, a Triangle coworking space
"Steve’s stopping here helps validate the work people here have been doing for years and years and years," said Lizzy Hazeltine, who focuses on connecting The Startup Factory’s portfolio of startups with outside investors.
The agenda for Rise of the Rest’s day in the Triangle included breakfast at the Governor's Mansion with business and civic leaders, stops at American Underground and HQ Raleigh, and a fireside chat with Case himself at the historic Carolina Theater in Durham.
Fireside chat with Case, moderated by Frank Gruber
The most electric event, however, was the pitch competition, a Rise of the Rest cornerstone. In front of a standing-room-only crowd, eight local startups - Tom and Jenny’s, Personalized Learning Games, ELXR Health, Stealz, Reveal Mobile, Antenna, RocketBolt, and Archive Social - had only minutes each to convince Case they deserved a $100,000 investment prize.
The Triangle’s spirit of collaboration pervaded the event, even among the competitors. "I’m just really excited to see all the companies," said Andy Roth, Head of Customer Success at RocketBolt. As a startup community that started in Indianapolis, Verge is thrilled to see its non-valley brethren gain entrepreneurial momentum.
Keep an eye out for the #RiseOfRest hashtag on social media and from Archive Social, the winner of the $100,000 investment in North Carolina's Triangle. America is on the rise!
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7b6341c45ce0572f13b444cedb68df3e | https://www.forbes.com/sites/matthunckler/2015/08/17/how-this-hackathon-is-inspiring-students-to-better-education/ | How This Hackathon Is Inspiring Students To Better Education | How This Hackathon Is Inspiring Students To Better Education
HackingEDU is inspiring college students to hack their way to a better educational future. The organization's inaugural Hackathon is coming up on October 23-25th at the San Mateo Event Center in San Francisco and is set to be the largest educational hackathon event in the world, bringing over 1,000 young and ambitious hackers from all over the country together to improve the landscape of higher education, while competing for over $100,000 in prizes.
Their aim: to change the world.
Starting a Movement
The Hackathon is run by the 3 co-founders: Alex Cory, Kirill Satanovsky, and Jackie Zhang, and was created as part of the Google Summit during the summer of 2014. The summit tasked eleven students from various universities on the west coast to go back to their schools and put on small hacking events there. Cory, Satanovsky, and Zhang knew this could be more than just a series of individual, isolated events. They envisioned something bigger, better, and world changing.
They decided to work together with the other ambassadors and put on one large event rather than several small ones, and thus the idea for HackingEDU was born.
Let's face it, the higher education system in the United States has some flaws. It is slow to adapt to changes that are plainly needed. That's why Cory, Satanovsky, and Zhang banded together to form HackingEDU to organize the Hackathon; they realized they are part of the university system, as all three of them are either students or consult in the higher education environment, and they and others like them have as much right to make a difference as anyone else.
They saw that they and other students are in a unique position to make a direct difference, because they are currently involved in the system. Their motto became, "If not them, then who? If not now, then when?" Now was the time to make a difference as far as they were concerned, which is why the Hackathon was put together so quickly after the Google Summit that inspired it.
What Makes This Hackathon Different from Other, Similar Events Across the Country?
By bringing the brightest minds together from all of the major universities in California and other west coast states and the country, HackingEDU is creating the opportunity for these minds to change higher education for the better through the use of technology. While the Hackathon is geared toward college students and marketed for them, it is actually open for anyone to attend. Any person who has good ideas for how to use technology to improve the higher education system is welcome, which makes it different from other events that are for students only.
The training day that gives participants opportunities to learn new technologies. It also allows participants the opporunity to gain direct experience with the technologies the event sponsors are using. This preparation lets participants be better prepared to demonstrate what they learned at the Hackathon when they present their ideas to leaders in the higher education community.
Hacking into the Future of Higher Education
As far as Cory, Satanovsky, and Zhang are concerned, this is just the beginning for the HackingEDU Hackathon. The organization is building a dynamic community of people from all walks of life...students, education professionals and businesses...who are passionate about transforming higher education for the better. These are people who will continue working together into the future to bring their innovative ideas to life and make them a reality for the world of higher education in this country.
If you ask HackingEDU's founders why growing the Hackathon is so important to them, they aren't shy about sharing. They know higher education is our nation's future, and they and a few other enterprising individuals want to make it the best it can be. Hackathon provides the platform for them to transform it in an environment where the best ideas can be incubated and implemented, benefiting generations of university students and instructors.
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be82c9ba8972b547bfe0f91277a03603 | https://www.forbes.com/sites/matthunckler/2016/05/17/is-neatso-the-uber-of-home-cleaning/ | Is Neatso The Uber Of Home Cleaning? | Is Neatso The Uber Of Home Cleaning?
Piggybacking on the growth of on-demand apps and a $15 billion home cleaning market, North Carolina startup Neatso wants to be the Uber of home cleaning. Driven by market need as well as a personal connection to the industry, Neatso hopes to penetrate the vibrant apartment market and spread from there. But will the app learn the lessons of its predecessors and deliver a positive experience for users and home cleaning professionals?
How Neatso Works
Neatso began when founders tried to refer their cleaning lady to friends and found that trying to coordinate schedules via text message was too inconvenient.
Attracted to the on-demand app idea, they sat down Jennifer, their "maid," and "picked her brain about the challenges she was facing" and what would make her life easier.
Using Jennifer's suggestions, they then built Neatso. Users can download the app, sign in, select their cleaning needs, and receive a quote for the cost. Quotes vary by level of services provided and size of the home.
If users want to move forward, they can confirm the cleaning and Neatso will match them with a home cleaner who has availability. Users cannot pick who cleans for them, a fact that may bother people who want a say over who comes to their home.
Once a cleaning is scheduled, users can provide special instructions in app. Neatso founders believe Millennial users would rather tell the app to "fold my laundry" than leave a note for an actual human.
After, users can rate their cleaning on a 1-5 scale and provide feedback. They can set up recurring cleanings or use the service as sporadically as they want.
Cleaners receive a flat rate of $20 per hour, and are paid within 48 hours.
Neatso is targeting the apartment community in Raleigh, which boasts more than 120,000 units.
Even if they capture just 2,000 units, they believe they will have a good user base to grow from.
Will Neatso Deliver Satisfaction? That Depends
Neatso isn't the only app in the home cleaning sphere - and its predecessors have gotten into some hot water. Take Handy, an NYC-based startup that has a 3-year jump on Neatso.
Handy has received criticism from cleaners who felt penalties were steep if they needed to miss a scheduled cleaning. Since Handy uses tiered wages, their cleaners needed to get high reviews consistently to earn top dollar. Many workers found these policies "exploitative."
As of July 2015, Handy faces two lawsuits from three contractors who believe they should receive employee protection. One has to wonder, will Handy's hardships make VC's leery of investing in apps like Neatso?
Another area of concern is contractor vetting. It's one thing to have a creepy Uber driver. You can get out of the car. Neatso users are letting a stranger into their house when they are not home. Cue huge potential for things to go wrong.
Neatso does not say whether reviews will factor into employee pay or frequency of scheduling, but it's clearly a pain point for the industry. They would be smart to resolve these issues.
Another competitor in the home cleaning sphere, Homejoy, has received $40 million in startup funding. Despite funding, Homejoy struggles to find cleaners with enough experience to perform quality work. Experienced cleaners are dissatisfied with wages, which range from $14 to mid-$20's per hour, and some have decided they'd rather return to using Craigslist to find customers than use the app.
Neatso wants users and cleaners alike to remain happy with the service. They hope to expand customization options going forward, and even allow users to select a "green cleaning." Watching the pitch below, it seems clear their hearts are in the right place.
While Neatso may work for Jennifer, the founder's "maid," it needs to find enough staff to clean those 2,000 units and beyond.
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7151eca4e70afcb9340874a79cd36176 | https://www.forbes.com/sites/matthunckler/2017/02/20/emotional-intelligence-in-business-and-life/ | Emotional Intelligence: Your Secret Weapon For Success In Business And Life | Emotional Intelligence: Your Secret Weapon For Success In Business And Life
ashleyzahabian.com
Ashley Zahabian had never heard of emotional intelligence, or EQ for “emotional quotient,” before she was hospitalized for severe anorexia as a teenager. After her recovery, EQ became the cause that drove her and led her down a path to positively impact the lives of thousands of others.
“I was hospitalized because I lacked emotional intelligence,” Zahabian told me in a recent interview. Because being unable to control her own emotions almost cost her life, she has now devoted herself to educating others on EQ’s importance.
The idea of EQ was first made popular by psychologist Daniel Goleman in his 1995 book, Emotional Intelligence. It’s been steadily gaining recognition over the past two decades, but Zahabian thinks it hasn’t caught on fast enough.
In 2012, she started uploading educational videos to YouTube and Facebook to teach people about EQ and why they need it. She’s since grown her reputation as an EQ consultant and keynote speaker for startup organizations, universities, corporate businesses, and conferences around the world. She has presented alongside Gary Vaynerchuk, Eric Thomas and Grant Cardone, and Elite Daily cofounder Gerard Adams was so moved by a conversation with her that he wrote an article about EQ for Entrepreneur.com.
“This was a personal problem for me, and I solved it," Zahabian said. “Now I want to share my solution with the world.”
EQ and Your Instant Gratification Addiction
Shutterstock
Put simply, emotional intelligence is the ability to understand and control our own emotions and the emotions of other people. Zahabian is most interested in the self-control aspect of EQ, and for her, this broad definition doesn’t dive deep enough.
Her lessons focus on the importance of delayed gratification. As an example, she pointed to the famous Stanford Marshmallow Experiment from 1960. In the experiment, young children were given a single marshmallow and told they could either eat it immediately or wait to eat it. If they waited, they would get two marshmallows to eat.
In followup studies conducted years later, the children who waited—or delayed their gratification—had higher SAT scores, higher incomes, better marriages, and were happier overall. This means that people who can be patient and hold out for more reap bigger and better rewards in pretty much all avenues of life.
The problem is that we’re all hardwired to crave immediate gratification, thanks to the neurotransmitter dopamine. We’re all literally addicted to the good sensations we get from eating a delicious meal, or closing a deal at work, or being intimate with a romantic partner. And as Zahabian can attest, pursuing immediate gratification can be dangerous. After all, her struggle with anorexia was essentially a battle with her addiction to feeling thin and attractive.
“Anything that’s worth it takes time, and it takes effort,” she said. “Anything that life says is good for you, there is a heavy price for it, and it’s dangerous when you don’t pay the price.”
Even when the situation isn’t life-or-death, chasing that instant high hurts us in the long run. Zahabian gave another example of a salesperson trying to make a sale:
“You don’t feel like prospecting, and instead of delaying the gratification of closing a sale, you keep calling and calling the same people, or you keep using other people’s leads...You don’t want to do the work so that you can get a bigger reward later, so you end up having lower results,” she said.
How to Improve Your EQ
ashleyzahabian.com
Once Zahabian started researching emotional intelligence and discovered how critical it is to success, she was shocked to discover that EQ still doesn’t get much attention in universities and businesses.
“Statistics from Harvard, Stanford, and Carnegie Foundation show that 85–87% of our success accounts from soft skills, emotional intelligence, and personal skills, yet we only pay attention to them 10% of the time,” Zahabian said. “It was so backwards to me.”
She decided she would not only teach people about EQ, but also teach them how to improve their EQ. This was the root of her business as a motivational speaker.
The best way to be more emotionally intelligent, Zahabian says, is to stop and question your feelings before you act. Think about why you really want something you’re craving. Is it actually something that’s good for you, or are you just giving into your immediate gratification addiction?
If you’re considering doing something that will only feel good right now, then maybe you shouldn’t do it. The long route—the route that takes time and effort—is always the better route.
How to Use EQ to Build a Better Business
Shutterstock
As mentioned above, this doesn’t just apply to your personal life. It’s relevant for businesses, too. Zahabian had some especially interesting things to say about the need for businesses to invest in and develop their young employees.
“Every business is in the business of building people,” Zahabian said. “If you cannot build people, you can’t do anything. Building people requires delayed gratification...It requires regulating emotion and controlling behavior, because it is not easy to build somebody who is a little bit under you, because it takes patience, it takes self-management, it takes leadership.”
As a founder or entrepreneur, it's important to learn more about your own emotional intelligence and work to increase it. Think about why you want the things you want and whether or not they’ll be good for you or your business in the long run. Practice saying “no” to yourself. And above all, don’t give into the temptation of immediate gratification.
“Every time that you invest in emotional intelligence, your outcome will be ten times better,” Zahabian said.
What’s Next for Ashley
Zahabian has already done a lot to build global awareness around EQ. She’s spoken all around the U.S., as well as in London, Canada, and Asia. Chris Middleton of Middleton Global Consulting has vouched for her, complimenting “her acumen as an unusually bright and competent business professional and as a thought leader in...emotional intelligence.”
And she has a lot more planned. She’s working on her own book about EQ, called Emotional Intelligence: It’s More Than Just You, which you can expect to hear more about in the future. She’s also teaching a course on EQ this year at the Feliciano School of Business at Montclair State University in New Jersey, and possibly at other schools in the future.
Zahabian is continuing her research on EQ and the real-life effects it has in company settings. In fact, she’s currently running a study with a financial services business on Wall Street to see how training their employees on emotional intelligence will affect their productivity. The results of the study will give her valuable data and help her refine what she teaches going forward.
You can learn more about Zahabian at her personal website, or connect with her on Facebook, Instagram, or Twitter, and follow her journey as it continues to unfold for this young entrepreneur.
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