At $28,000 a Dose, How Effective Is Acthar?

By Jonathan J. Darrow

In a well-researched, recent post, Patrick O’Leary addresses the FDA’s efficacy requirements as applied to an old drug, Acthar (corticotropin), that was first approved in 1952 and granted an orphan designation in 2010 for the treatment of infantile spasms. The initial approval therefore occurred before the Drug Amendments of 1962, which instituted a “new” statutory requirement of efficacy (more on this below). O’Leary points out that Acthar’s “grandfather” status does not entirely exempt it from the FDA’s efficacy requirements, and that the drug did survive an efficacy evaluation under the DESI program. But how effective is Acthar?

Neither O’Leary nor the New York Times article on which his post is based dig very far into the clinical trial data accepted by the FDA as supporting the efficacy of the drug as a treatment for infantile spasms, and I was curious to know what the evidence says about Acthar in this regard. Clinical trial data is presented—or perhaps more accurately, “buried”—in Section 14 of a drug’s FDA-approved label; in the case of “H.P. Acthar Gel” (NDA 022432), that label can be found here. What does the clinical trial data reveal?  The section is brief, just half a page, and notes that of “[t]hirteen of 15 patients (86.7%) responded to Acthar Gel as compared to 4 of 14 patients (28.6%) given prednisone (p<0.002).”  Nonresponders were then given the other treatment, with the following results. “Seven of 8 patients (87.5%) responded to H.P Acthar Gel after not responding to prednisone,” while “[o]ne of the 2 patients (50%) responded to the prednisone treatment after not responding to Acthar.”  As the p-value (0.002) indicates, the first figures, at least, are statistically significant.  These figures were also better than I expected: 86.7% efficacy with Acthar does seem much better than 28.6% efficacy with prednisone.  Read More

Regulatory Concepts in the News, Part I: FDA Efficacy Standards for Old Drugs

By Patrick O’Leary

While reading some of the great articles from the health section of the New York Times over the holidays it struck me that such articles, in their need to be concise and accessible, often give only passing treatment to regulatory concepts that can be fundamental to the story. Accordingly, I thought it might be useful to write a series of posts digging down a bit deeper into some of the regulatory foundations of health stories that percolate up to public attention through the news. In this post I’ll begin by looking at an interesting point relating to drug efficacy standards raised by an article about a newly expensive (but decades-old) drug.

In Andrew Pollack’s “Questcor Finds Profits, at $28,000 a Vial” we read that a drug called Acthar, first approved by the FDA in 1952 and used primarily to treat rare infantile spasms, has in recent years become a very expensive and (for it’s maker) lucrative treatment for conditions ranging from multiple sclerosis to rheumatologic conditions. The article is worth a read for its thoughtful discussion of drug pricing, but it also makes passing reference to a some important regulatory concepts that bear further examination. One issue that particularly stood out to me was Pollack’s statement that Questcor, Acthar’s manufacturer, has been able to market the drug for a variety of uses “without being required to prove that the drug actually works” because it was “essentially grandfathered” into an anachronistic efficacy standard by being “approved for use in 1952, before the [FDA] required clinical trials . . . .” On first read, that sounds fairly alarming, so I thought it might be worthwhile to unpack the law around such “grandfathered” drugs a little. While it is true that FDA did not require proof of effectiveness for new drugs until lawmakers included this requirement in the Drug Amendments of 1962, it isn’t the case that pre-1962 drugs simply get a free pass on proving effectiveness. The truth, as one might expect, is somewhat more complicated. Read More

Upcoming Event 01/17 – Food & Drug Law: Past, Present & Future

SAVE THE DATE!

Food & Drug Law: Past, Present & Future
Celebrating Peter Barton Hutt’s 20 Years (thus far) at HLS

Thursday, January 17, 2013
Wasserstein 2019; Milstein West AB

Harvard Law School
4:00pm (reception to follow at 5:30)

Peter Barton Hutt has worked at the Washington, DC law firm of Covington & Burling, specializing in Food and Drug Law, for more than five decades. He has represented clients in administrative, legislative, executive, and judicial settings. He began his law practice with the firm in 1960 and is now Senior Counsel; between 1971 to 1975, he was Chief Counsel for the Food and Drug Administration. The Best Lawyers in America selected Mr. Hutt as the 2013 FDA Lawyer of the Year for Washington, DC. Since 1994, Mr. Hutt has taught Food and Drug Law during Winter Term at Harvard Law School, covering all aspects of government regulation of food and drugs from ancient times to present.

Introductions and Welcome

Martha Minow, HLS Dean

Tributes to Professor Hutt

  • I. Glenn Cohen, Assistant Professor, Harvard Law School; Faculty Co-Director, Petrie-Flom Center
  • Theodore Ruger, Professor of Law, Penn Law School
  • Lewis Grossman, Professor of Law, American University Washington College of Law

Reflections
Peter Barton Hutt

Questions and Discussion

Dean Minow and Audience

For questions, contact petrie-flom@law.harvard.edu, 617-496-4664

Co-sponsored by the Petrie-Flom Center and the HLS Dean’s Office

 

Researchers to Lawmakers: Naloxone Distribution to Prevent Overdose Death is Cost-Effective

By Scott Burris

Phil Coffin and Sean Sullivan have published a cost-effectiveness study of interventions that equip heroin users and others to administer naloxone in the event of a witnessed opioid overdose.  Naloxone is the standard antidote, and can easily be administered by lay people with a minimum amount of training.  Family members and friends of opioid users can quickly get the drug into an overdosing user via injection or a nasal spray. In an accompanying editorial, top brass at NIDA and FDA sum up the news like this: the study

“represents a significant step in the evolution of the science in this area: a detailed analysis of the cost-effectiveness of overdose intervention with naloxone administration for heroin abusers. The authors suggest that lay naloxone administration is likely to be highly cost-effective in this setting, a robust finding that holds up under various assumptions. Future analyses that extend their findings to the setting of prescription opioids would be welcome.”

The editorial flags one of the major legal issues that gets in the way of wider naloxone distribution – its status as a prescription drug approved for use by injection. Changing this is a torturous regulatory process. In the short term, though, lawmakers can do a lot to get distribution going where it is needed.  As of July of 2012, eight states had passed laws to clearly authorize or otherwise reduce legal barriers to the prescription of naloxone to drug users and other potential good Samaritans. That leaves 42 states where programs may have trouble operating out of concerns related to prescribing a drug for a lay person to administer. LawAtlas covers the law and has examples of the legislative approaches these states have taken.

One more thing: evidence that naloxone distribution looks to be cost-effective ought to motivate lawmakers to consider these programs.  Many places don’t have them at all: a study published last year in MMWR reported, among other things, that “Nineteen (76.0%) of the 25 states with 2008 drug overdose death rates higher than the median and nine (69.2%) of the 13 states in the highest quartile did not have a community-based opioid overdose prevention program that distributed naloxone.”  In others, programs are operating but with little or no public funding to purchase naloxone, whose price has been rising precipitously (that’s another story about our creaking system for producing essential medicines).

‘Frankenfish’ far less scary than fast food

By Art Caplan [cross-posted from his NBCNews Vitals column]

Two big events recently took place in the world of food: The Food and Drug Administration decreed that genetically engineered salmon wouldn’t harm the environment and McDonald’s announced that its McRib sandwich is back on the menu.

The FDA’s announcement paves the way for the first approval of a genetically engineered animal for humans to eat – and it was met with a good deal of highly critical wailing and groaning by Consumer’s Union, National Geographic and many other advocacy groups who are wary of genetically engineered food.

The McRib’s return was greeted with a few snickers by late night comedians and overwhelmingly happy faces on the millions of Americans who eat at one of the 13,000 McDonald’s restaurants from Maine to Hawaii every day. This, as my grandmother would have said in Yiddish, is “fakakta”—completely screwy.

If you like salmon, and I do, should you worry much about the safety of eating genetically engineered salmon?  No. The FDA said it could not find any valid scientific reason to prohibit the sale of the fish.

If you like the McRib, and I do, should you worry a lot about eating it?  Oh yeah.

Keep reading…

Bad to the Bone

By Christopher Robertson

I just came across this excellent story by Mina Kimes, which gives a detailed chronicle of how the lines between physician discretion, off-label promotion, and human subjects research can be blurred by an aggressive manufacturer, in a context where life or death is on the line (bone cement used in spine surgery).  The article also suggests themes about medical malpractice, products liability, and physicians’ conflicts of interest too.

Today’s the Day – Abstracts Due for Petrie-Flom Center Annual Conference

Last call! Abstracts for the Petrie-Flom Center’s annual conference – this year entitled “The Food and Drug Administration in the 21st Century” – are due today.  This one and a half day event will take place Friday and Saturday, May 3-4, 2013, at Harvard Law School in Cambridge, Massachusetts.

For further details, see the Call for Papers/Presentations.

Film Review: How to Survive a Plague

By Suzanne M. Rivera

How to Survive a Plague is a moving chronicle of the onset of the AIDS epidemic as seen through the lens of the activists who mobilized to identify and make available the effective treatments we have today.  Beginning at the start of the epidemic, when little was known about the HIV virus and even hospitals were refusing to treat AIDS patients out of fear of contagion, the film follows a group of leaders in the groups ACT-UP and TAG.  Using existing footage interspersed with current-day interviews, it tells the story of how patients and concerned allies pushed the research community to find a way to treat what was then a lethal disease.

The film’s portrayal of the U.S. Government, specifically then-President George H. W. Bush and high ranking officials in the Food and Drug Administration, is damning.  As hundreds of thousands of people became infected with HIV and the death toll rose, prejudice against marginalized groups (especially gay men, IV drug users) contributed to a lack of urgency about the need to learn how stop the spread of the virus and how to treat the opportunistic infections that killed people with full-blown AIDS.  In contrast, footage of demonstrations, meetings, and conferences highlights the courage of the activists who risked and endured discrimination, beatings and arrests to bring attention to the need for more research.

But How to Survive a Plague is more than a documentary about the power people have to make change when they join together to demand action.  It also is a provocative commentary about unintended consequences.  I saw the film while attending the annual Advancing Ethical Research Conference of Public Responsibility in Medicine and Research (PRIM&R).  In that context, I was especially interested in the way How to Survive a Plague highlights an interesting ethical issue in clinical research. Namely, the problem of protecting people so much from research risks that the protection itself causes harm. Read More

The Future of Biomedical Research Funding

By Patrick O’Leary

As I’ve written about previously on this blog, the consequences for the FDA of budget sequestration under the Budget Control Act of 2011 could be fairly severe (as well as raise some interesting legal questions). In a recent Online First piece for the Journal of the American Medical Association (JAMA), Hamilton Moses and E. Ray Dorsey note that sequestration would also have a serious impact–to the tune of $2.5 billion–on the National Institutes of Health (NIH), the primary source of public funding for biomedical research in the United States.

While Doctors Moses and Dorsey acknowledge that the immediate consequences of such a cut would primarily affect young researchers and new applicants for funding, “exacerbat[ing] tensions between large infrastructure projects . . . and small investigator-initiated grants, which historically have been the primary source of new clinical insights,” they also argue that sequestration presents an opportunity to reevaluate our emphasis on publicly funded biomedical research. In their telling, sequestration would be just the most recent step in a nearly decade-long trend of reducing federal funding, a trend that “presents an opportunity to reshape biomedical research.” Moses and Dorsey call for new private sources of research support, ranging from specialized financial instruments like Biomedical Research Bonds to an increased role for public charities and private foundations. The future of biomedical research, they argue, will be built on the private sector, not the federal government.

The challenges of shifting the burden of funding research to the private sector are many, of course. One particularly challenging question is whether private funds could effectively replace NIH’s significant role in funding “basic” research. Bhaven N. Sampat’s new article “Mission-Oriented Biomedical Research at the NIH” in Research Policy provides some context for the scale of the problem. Citing a 2010 study by Dr. Dorsey himself, Sampat notes that although NIH funding accounts for only about a third of U.S. biomedical research funding, “there is a sharp division of labor, with NIH funding concentrated further upstream, on ‘basic’ research than private sector funding” from private sector pharmaceutical, biotechnology, and medical device firms. Although the role of private foundations has grown in recent years, Sampat notes that NIH funding continues to exceed all such funding “by a factor of six . . . .” Assuming we continue to value basic research, the capacity and willingness of private actors to fund such research thus remains a major question mark.

Reminder: Abstracts for Petrie-Flom Annual Conference Due 12/14/12

Another reminder: abstracts for the Petrie-Flom Center’s annual conference – this year entitled “The Food and Drug Administration in the 21st Century” – are due one week from today, no later than December 14, 2012.  This one and a half day event will take place Friday and Saturday, May 3-4, 2013, at Harvard Law School in Cambridge, Massachusetts.

For further details, see the Call for Papers/Presentations.