Results for “fda” 465 found
Japan Liberalizes Regenerative Medicine
Japan is liberalizing its approval process for regenerative medicine:
…Regenerative medicines in Japan can now get conditional marketing approval based on results from mid-stage, or Phase II, human trials that demonstrate safety and probable efficacy. Once lagging behind the United States and the European Union on approval times, there is now an approximately three-year trajectory for approvals, according to Frost’s Kumar. That compares with seven to 10 years before.
…Around the world, companies have also faced setbacks while pushing such treatments. In the U.S., Geron Corp., which started the first nation-approved trial of human embryonic stem cells, ended the program in 2011, citing research costs and regulatory complexities.
…While scientists globally have worked for years in this field, treatments have been slow to come to market. But there is hope in Japan that without the political red tape, promising therapies will emerge faster and there will be speedier rewards.
Japan is liberalizing because with their aging population treatments for diseases like Alzheimer’s and Parkinson’s disease are in high demand. Under the new system, a firm with a gene or regenerative therapy (e.g. stem cells) can get conditional approval with a small trial. Conditional approval means that the firm will be able to sell its procedure while continuing to gather data on efficacy for a period of up to seven years. At the end of the seven year period, the firm must either apply for final marketing approval or withdraw the product. The system is thus similar to what Bart Madden proposed for pharmaceuticals in Free to Choose Medicine.
Due to its size and lack of price controls, the US pharmaceutical market is the most lucrative pharmaceutical market in the world. Unfortunately, this also means that the US FDA has an outsize influence on total world investment. The Japanese market is large enough, however, that a liberalized approval process if combined with a liberalized payment model could increase total world R&D.
Breakthroughs made in Japan will be available for the entire world so we should all applaud this important liberalization.
Hat tip: Michael Mandel.
Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection
The Nature article is here. The FT put it differently: “Scientists make breakthrough in search for universal flu vaccine” Here are many other articles on the same.
And how long did it take us, starting more or less from scratch, to make that Ebola vaccine?
Is it possible that our vaccine development capacity is seriously better than say ten years ago?
Are the biggest potential winners China, India, Indonesia, and Nigeria?
For a relevant pointer I thank J.
The economics of biosimilars
If I understand correctly, a biologic is “any medicinal product manufactured in, extracted from, or semisynthesized from biological sources,” and a biosimilar is a copy of a biologic. Think of a biosimilar as harder to make than a generic drug and also requiring separate FDA approval. Here is Wikipedia:
Unlike the more common small-molecule drugs, biologics generally exhibit high molecular complexity, and may be quite sensitive to changes in manufacturing processes. Follow-on manufacturers do not have access to the originator’s molecular clone and original cell bank, nor to the exact fermentation and purification process, nor to the active drug substance. They do have access to the commercialized innovator product.
Here is a Rand piece on the potential cost savings from biosimilars (pdf), but in percentage terms they do not become nearly as cheap as generic drugs, maybe 65-85% of the price of the original.
Zarxio was the first biosimilar approved by the United States, and the global biosimilars market could hit $55 billion by 2020. Here is yesterday’s FT story about biosimilars draining away sales.
Here is a paper by Blackstone and Fuhr:
Various factors, such as safety, pricing, manufacturing, entry barriers, physician acceptance, and marketing, will make the biosimilar market develop different from the generic market. The high cost to enter the market and the size of the biologic drug market make entry attractive but risky.
Will cell therapies, which are relatively new and also hard to copy with biosimilars, save Big Pharma from the forthcoming patent cliff?
Biosimilars will become a bigger issue soon:
There are 11 biologic drugs that will face biosimilar competition in the next several years, according to data compiled by Evercore ISI. These drugs, which treat ailments from cancer to rheumatoid arthritis, raked in more than $50 billion combined in 2014.
The FDA is outlining biosimilar approval pathways, although the issue seems to be receiving almost zero attention from the outside world.
Are S&P 500 firms now 5/6 “dark matter” or intangibles?
Justin Fox started it, and Robin Hanson has a good restatement of the puzzle:
The S&P 500 are five hundred big public firms listed on US exchanges. Imagine that you wanted to create a new firm to compete with one of these big established firms. So you wanted to duplicate that firm’s products, employees, buildings, machines, land, trucks, etc. You’d hire away some key employees and copy their business process, at least as much as you could see and were legally allowed to copy.
Forty years ago the cost to copy such a firm was about 5/6 of the total stock price of that firm. So 1/6 of that stock price represented the value of things you couldn’t easily copy, like patents, customer goodwill, employee goodwill, regulator favoritism, and hard to see features of company methods and culture. Today it costs only 1/6 of the stock price to copy all a firm’s visible items and features that you can legally copy. So today the other 5/6 of the stock price represents the value of all those things you can’t copy.
Check out his list of hypotheses. Scott Sumner reports:
Here are three reasons that others have pointed to:
1. The growing importance of rents in residential real estate.
2. The vast upsurge in the share of corporate assets that are “intangible.”
3. The huge growth in the complexity of regulation, which favors large firms.
It’s easy enough to see how this discrepancy may have evolved for the tech sector, but for the Starbucks sector of the economy I don’t quite get it. A big boost in monopoly power can create a larger measured role for accounting intangibles, but Starbucks has plenty of competition, just ask Alex. Our biggest monopoly problems are schools and hospitals, which do not play a significant role in the S&P 500.
Another hypothesis — not cited by Sumner or Hanson — is that the difference between book and market value of firms is diverging over time. That increasing residual gets classified as an intangible, but we are underestimating the value of traditional physical capital, and by more as time passes.
Cowen’s second law (“There is a literature on everything”) now enters, and leads us to Beaver and Ryan (pdf), who study biases in book to market value. Accounting conservatism, historical cost, expected positive value projects, and inflation all can contribute to a widening gap between book and market value. They also suggest (published 2000) that overestimations of the return to capital have bearish implications for future returns. It’s an interesting question when the measured and actual means for returns have to catch up with each other, what predictions this eventual catch-up implies, and whether those predictions have come true. How much of the growing gap is a “bias component” vs. a “lag component”? Heady stuff, the follow-up literature is here.
Perhaps most generally, there is Hulten and Hao (pdf):
We find that conventional book value alone explains only 31 percent of the market capitalization of these firms in 2006, and that this increases to 75 percent when our estimates of intangible capital are included.
So some of it really is intangibles, but a big part of the change still may be an accounting residual. Their paper has excellent examples and numbers, but note they focus on R&D intensive corporations, not all corporations, so their results address less of the entire problem than a quick glance might indicate. By the way, all this means the American economy (and others too?) has less leverage than the published numbers might otherwise indicate.
Here is a 552 pp. NBER book on all of these issues, I have not read it but it is on its way in the mail. Try also this Robert E. Hall piece (pdf), he notes a “capital catastrophe” occurred in the mid-1970s, furthermore he considers what rates of capital accumulation might be consistent with a high value for intangible assets. That piece of the puzzle has to fit together too. This excellent Baruch Lev paper (pdf) considers some of the accounting issues, and also how mismeasured intangible assets often end up having their value captured by insiders; that is a kind of rent-seeking explanation. See also his book Intangibles. Don’t forget the papers of Erik Brynjolfsson on intangibles in the tech world, if I recall correctly he shows that the cross-sectoral predictions line up more or less the way you would expect. Here is a splat of further references from scholar.google.com.
I would sum it up this way: measuring intangible values properly shows much of this change in the composition of American corporate assets has been real. But a significant gap remains, and accounting conventions, based on an increasing gap between book and market value, are a primary contender for explaining what is going on. In any case, there remain many underexplored angles to this puzzle.
Addendum: I wish to thank @pmarca for a useful Twitter conversation related to this topic.
Assorted links
1. Book preview for 2015. Good stuff, including volume four of Knausgaard, a new Stephenson, a new Gaiman, a new Ishiguro, a Philip Glass memoir, perhaps the Niall Ferguson book on Kissinger will be interesting too. Here is another preview list. And who was nominated for a literary Nobel Prize in 1964.
2. The pick-up culture that is Chinese.
3. Another (right-wing?) view on why the leading public intellectual economists are left-wing. And more from Krugman.
4. Voodoo and Haitian mental health. And the culture that is Singapore.
Printing Cancer Killing Viruses
Cell biologist Andrew Hessel of Autodesk is designing viruses in software to attack a specific individual’s cancer and then using DNA Printers to create the viruses as a drug. Here from an interview with New Scientist (gated).
It’s really about making a specific medicine tailored to one person–“N-of-1” medicine–rather than try to make it a best fit for a whole population. My vision is to create a personalized treatment that can be made in a day by printing bespoke cancer-fighting viruses.
I’m not fully convinced by his economic model but it may be useful as a vision-goal:
I see the business model shifting away from the blockbuster-drug model of the pharma industry–getting the best product for the most people and charging the most for it–to more of a Netflix model, in which you might purchase a subscription for all-that-you-need medicine to manage your cancer.
…I’m pretty sure I can get the virus printing costs down to a dollar a dose. The virus itself is designed by algorithms using diagnostic data from the patient. That info is put into a program that will design the cancer-fighting virus, so the cost of design is cheap. Then there’s testing, and there is no simpler test than on the patient’s own cancer cells in a dish. So that whole process should cost less than $100 end-to-end. If you are on a cancer subscription model paying $100 a month, I see that as ultimately profitable.
Hessel is also far too sanguine about the FDA who he thinks will allow this under “compassionate use.” No way – not today when the FDA prohibits 23andMe from even providing information about DNA and its probable consequences, see my post Our DNA, Our Selves. To make this a reality we will need scientific breakthroughs and also A New FDA for the Age of Personalized Medicine.
Pharmaceutical regulation is getting tougher
From Diana Carew at the Progressive Policy Institute:
…the number of ‘restrictions’ on drug companies increased by 767, or 40% since 2000. This represents a substantial rise in the overall regulatory burden of pharmaceutical companies, which must allocate resources to ensure regulatory compliance. The word “restriction” refers to command clauses such as “shall” and “must,” as contained in sections of the Code of Federal Regulations related to the FDA.
The full study is here (pdf).
Assorted links
1. How Facebook is shaping the news.
2. 1959 Isaac Asimov short essay on how to stimulate creativity.
3. “The Army is conducting a reverse auction for Catholic priest services.”
4. Another superb Michael Hoffman review, this time of Martin Amis on Auschwitz.
5. Ryan Avent on how bad is Amazon? And Joshua Gans on Krugman on Amazon.
6. Richard Preston on Ebola. And David Brooks on why Ebola has taken over our minds.
The new Obama plan to combat antibiotic overuse
The Obama administration on Thursday announced measures to tackle the growing threat of antibiotic resistance, outlining a national strategy that includes incentives to spur the development of new drugs, tighter stewardship of existing ones and a national tracking system for antibiotic-resistant illness. The actions are part of the first major federal effort to confront a public health crisis that takes at least 23,000 lives a year.
The full story is here.
The Hill has more detail. It is an executive order:
The president’s directive creates the Task Force for Combating Antibiotic-Resistant Bacteria, co-chaired by the secretaries of Defense, Agriculture and Health and Human Services.
The group is charged with implementing a plan to track and prevent the spread of antibiotic-resistant bacteria, promote better practices for the use of current drugs and push for a new generation of antibiotic medications.
To that end, the White House on Thursday announced a $20 million prize “to facilitate the development of rapid, point-of-care diagnostic tests for healthcare providers to identify highly resistant bacterial infections.”
The added incentive and the timeframe given to the task force indicate the urgency with which the administration is acting, said Dr. Eric Lander, who co-chairs the President’s Council of Advisors on Science and Technology.
“This is a pretty tight timeline to now come up with a national game plan,” Lander said.
There is also this:
In December, the Food and Drug Administration (FDA) unveiled a plan to phase out the use of antimicrobials for the purpose of fattening chickens, pigs or other animals destined for human consumption. But the plan relies in part on voluntary industry cooperation, and advocates argue the government’s efforts are lagging behind even some industry players.
Here is the new full 78 pp. report to the President on antibiotic resistance (pdf).
This initiative — or its failure — is potentially a more important health issue than Obamacare, yet it will not receive 1/1000th of the attention. Without reliable antibiotics, a lot of now-routine operations would become a kind of lottery.
Here are previous MR posts on antibiotic resistance. I would note it is difficult to judge such a plan at the current level of detail. It is better than nothing, but any initial plan is going to be not nearly enough, relative to an ideal. By the way, Alex tells me there is also a British prize, discussed here.
Co-opting Regulation for Profit
Regulations often increase monopoly power. Indeed, increasing monopoly power is often why regulations are enacted. In other cases, however, ostensibly neutral regulations are co-opted by entrepreneurs who spot an opportunity to leverage the regulation for profit. Derek Lowe points us to an interesting case of the latter involving drug pricing and the FDA.
Retrophin recently purchased the marketing rights to the drug Thiola and they are increasing the price from $1.50 per pill to over $30 per pill. Surprisingly, Thiola is off-patent. Ordinarily, we would expect such a large price increase to be met with entry and price pushed to marginal cost. To enter into the market, however, a generic producer must prove bio-equivalence which requires that the generic producer obtain a small quantity of the branded drug. Branded drug firms don’t like competition from generics and they try to impede the process but it’s typically not a big deal for a generic producer to obtain some of the branded drug for their bio-equivalence trials.
In 2007, however, the FDA was officially authorized to approve drugs conditional on the firm implementing a Risk Evaluation and Mitigation Strategy (REMS). The FDA approved thalidomide, for example, only if physicians signed a patient-physician agreement and enrolled each of their patient’s directly with the producer. Indeed, a unique prescription authorization number was required for each prescription which could be filled only at specially authorized pharmacies. The idea, of course, was to prevent anyone from taking thalidomide during pregnancy. The purpose of the regulation was probably not to create monopoly power but it didn’t take firms long to realize that REMS regulations could be co-opted. Simply put, a REMS agreement can make it illegal for generic firms to obtain a sample of the branded drug through ordinary channels. In the thalidomide agreement, for example, it’s even the case that all unused thalidomide must be returned to the producer! Retrophin is hoping to use a similar REMS strategy to keep generic competitors out of the market for Thiola.
Addendum: Derek’s post aroused the ire of the CEO of Retrophin and may have gotten him banned from reddit.
The decline of the week-long vacation (America fact of the day)
Nine million Americans took a week off in July 1976, the peak month each year for summer travel. Yet in July 2014, just seven million did. Keeping in mind that 60 million more Americans have jobs today than in 1976, that adds up to a huge decline in the share of workers taking vacations.
Some rough calculations show, in fact, that about 80 percent of workers once took an annual weeklong vacation — and now, just 56 percent do.
That is from Evan Soltas, there is more here. And Evan offers a bit more here.
Innovation Breakdown
From my review today in the WSJ of Innovation Breakdown by Joseph Gulfo:
Yo is a smartphone app. MelaFind is a medical device. Yo sends one meaningless message: “Yo!” MelaFind tells you: “biopsy this and don’t biopsy that.” MelaFind saves lives. Yo does not. Guess which firm found it easier to put their product in consumers hands? Oy.
In “Innovation Breakdown: How the FDA and Wall Street Cripple Medical Advances,” Joseph Gulfo tells the tumultuous history of MELA Sciences, the company that invented MelaFind. When Dr. Gulfo joined the firm as president and CEO in 2004, the company’s brilliant team of scientists had spent many years and tens of millions of dollars to develop MelaFind, a “camera with a brain”—optical technology that would scan potential melanomas in multiple spectra and then, using sophisticated algorithms and large datasets, diagnose which were most likely to be cancerous.
MELA Sciences conducts an extensive clinical trial according to a protocol agreed on by the FDA and all looks good. After the clinical trial is completed, however, the FDA backs away from the protocol and comes out against MelaFind.
…The title of Dr. Gulfo’s book is “Innovation Breakdown” but “Innovator’s Breakdown” might have been more apt. The letter sent the author into survival mode. He battled the FDA, calmed investors, and defended against the lawsuit all while trying to keep the company afloat. Under stress, Dr. Gulfo’s health began to decline: He lost 29 pounds, his hair began to fall out, and the pain in his gut became so intense he needed an endoscopy. When his wife begged him to quit, he refused. They turned into roommates. “We were nothing more than cordial. I basically shut my wife out of my life,” he writes.
…The climax to this medical thriller comes when, in “the greatest 15 minutes of [his] life,” Dr. Gulfo delivers an impassioned speech, à la “Twelve Angry Men,” to the FDA’s advisory committee. The committee voted for approval, 8 to 7, and, perhaps with the congressional hearing in mind, the FDA approved MelaFind in September 2011.
It was a major triumph for the company, but Dr. Gulfo was beat. He retired from the company in June 2013—just in time to save his marriage.
Yet remarkably, given his experience, Mr. Gulfo writes that he still believes in a strong FDA. He argues in the book that better “leadership” and a few tweaks to existing rules can fix the problem. He’s wrong.
Compare MelaFind’s experience in the U.S. with its reception in Europe: MelaFind was submitted for marketing approval in Europe in May 2011. It was approved just five months later. One key reason for Europe’s efficient approval process is that European governments don’t review medical devices directly. Instead they certify independent “notified bodies” that specialize and compete to review new products. The European system works more quickly than the U.S. system, and there is no evidence that it results in reduced patient safety. Rather than tweak the current system, why doesn’t the U.S. just adopt the European model and call it a day? Our health and our economy would be better off for it.
Google’s Sergey Brin recently said that he didn’t want to be a health entrepreneur because “It’s just a painful business to be in . . . the regulatory burden in the U.S. is so high that I think it would dissuade a lot of entrepreneurs.” Mr. Brin won’t find anything in Dr. Gulfo’s book to persuade him otherwise. Until we get our regulatory system in order, expect a lot more Yo’s and not enough life-saving innovations.
The FT summer book reading list
War: What is it Good for? The Role of Conflict in Civilisation, from Primates to Robots, by Ian Morris, Profile, RRP£25/ Farrar, Straus and Giroux, RRP$30
In this remarkable book, historian Morris argues not only that war is a source of technological advance but that it brings peace. Through war, more powerful and effective states emerge and these in turn do not merely offer the blessings of peace, but impose it. The thesis is disturbingly persuasive. But, in a nuclear age, the great powers will have to try something else.
The full list is here, possibly gated. They also recommend the Adam Tooze book on the post WWI era, which I now have finished and really like and also find to be quite Sumnerian. Adam Minter’s Junkyard Planet is an excellent read as well.
All hail Khan!
Congratulations to Razib Khan, the noted genetics blogger, on the birth of his son. Born just last week, Razib’s son is already making the news:
An infant delivered last week in California appears to be the first healthy person ever born in the U.S. with his entire genetic makeup deciphered in advance.
Razib, a graduate student at a lab at UC Davis in California, had some genetic material from his in-womb son from a fairly standard CVS test.
When Khan got the DNA earlier this year, he could have ordered simple tests for specific genes he was curious about. But why not get all the data? “At that point, I realized it was just easier to do the whole genome,” he says. So Khan got a lab mate to place his son’s genetic material in a free slot in a high-speed sequencing machine used to study the DNA of various animal species. “It’s mostly metazoans, fish, and plants. He was just one of the samples in there,” he says.
The raw data occupied about 43 gigabytes of disk space, and Khan set to work organizing and interpreting it. He did so using free online software called Promethease, which crunches DNA data to build reports—noting genetic variants of interest and their medical meaning. “I popped him through Promethease and got 7,000 results,” says Khan.
Promethease is part of an emerging do-it-yourself toolkit for people eager to explore DNA without a prescription. It’s not easy to use, but it’s become an alternative since the FDA cracked down on 23andMe.
Craig Venter was the first person to have his genome sequenced, that was in 2007. Now, just seven years later, costs have fallen by a factor of 10,000. Personal genome sequencing is going to become routine regardless of the FDA.
Why Vampires Live So Long
NYTimes: Two teams of scientists published studies on Sunday showing that blood from young mice reverses aging in old mice, rejuvenating their muscles and brains. As ghoulish as the research may sound, experts said that it could lead to treatments for disorders like Alzheimer’s disease and heart disease.
The key papers are here and here and here. Some of the papers are pointing to a specific protein but the last paper suggests that simple transfusions also work and that raises a number of issues of public policy. As Derek Lowe notes:
Since blood plasma is given uncounted thousands of times a day in every medical center in the country, this route should have a pretty easy time of it from the FDA. But I’d guess that Alkahest is still going to have to identify specific aging-related disease states for its trials, because aging, just by itself, has no regulatory framework for treatment, since it’s not considered a disease per se.
…You also have to wonder what something like this would do to the current model of blood donation and banking, if it turns out that plasma from an 18-year-old is worth a great deal more than plasma from a fifty-year-old. I hope that the folks at the Red Cross are keeping up with the literature.