Expedited FDA Approval for Breakthrough Therapies: Promises and Pitfalls

By Michael Young

In 2012, the FDA introduced a novel pathway for expedited review of breakthrough therapies. The ‘breakthrough-drug’ designation was carved out by the Food and Drug Administration Safety and Innovation Act (FDASIA), which provided for expedited development and review of any drug “intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.”  This pathway added to a variety of other accelerated FDA approval programs aimed at improving access to innovative, safer, or more effective therapies for serious medical conditions.

In a recent New England Journal of Medicine article, Jonathan Darrow, Jerry Avorn and Aaron Kesselheim examine the clinical consequences and ethical dimensions of the breakthrough-drug category, and raise a variety of vital questions about its implications for patients.

Read More

New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives

By Timo Minssen

Please find attached a ppt presentation on “New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives” given on March 7, 2014 at the Broad Institute of MIT and Harvard.  The presentation was followed by a discussion moderated by US patent attorney Melissa Hunter-Ensor, Partner at Saul Ewing, Boston.

I started out by emphasizing increasing problems of antimicrobial resistance (AMR) on a global level, providing new statistics and facts. This was followed by a discussion of main reasons for these alarming developments, such as inappropriate use in agriculture and medicine, insufficient precautions, lack of education, climate change, travel behavior, insufficient collaboration and funding of R&D, scientific complexities, and the problem that incentives provided by the traditional innovation system model often fail in the case of antibiotics.

Next the presentation focused on a variety of solution models that could be discussed to fight AMR. These include both conservational and preventive approaches comprising use limitations, increased public awareness, and better hygiene, but also reactive push & pull strategies, such as increased investments, new collaborative models for R&D in antibiotics, prizes, “sui generis” IP-related incentives, regulatory responses and new pathways for approval.

Read More

Video Debate: Richard Epstein and Ryan Abbott on FDA Involvement in Off-Label Drug Use

By Ryan Abbott

Video: Here.

On January 13, 2014 the Southwestern Law School Federalist Society student chapter hosted a debate about the FDA’s role in regulating off-label drug use featuring Professor Richard Epstein, the Laurence A. Tisch Professor of Law at NYU and the Kirsten Bedford Senior Fellow at the Hoover Institution, and Ryan Abbott, Associate Professor of Law at Southwestern Law School and Visiting Assistant Professor of Medicine at the David Geffen School of Medicine at UCLA.

Before a drug can be sold legally in the United States, the Food and Drug Administration (FDA) must approve it as safe and effective for a particular indication or use — the use then appears on the drug’s label. Federal law, however, allows doctors to prescribe drugs that the FDA has approved for one indication for any other indication, even though the FDA never evaluated the safety or efficacy of the drug for that use.

Off-label prescribing is an integral part of modern-day medicine. Patients may benefit when they receive drugs or devices in contexts not approved by the FDA. In fact, in some instances an off-label use may be the standard of care for a particular health problem. However, off-label prescribing can also harm patients, especially when an off-label use lacks a solid evidentiary basis.

For this reason, the FDA forbids drug companies from promoting their own products for off-label use, except for certain activities such as disseminating research literature and sponsoring educational programs. In recent years, civil and criminal actions against drug companies for illegal promotion for off-label use have proliferated, leading to many large settlements. For example, in July 2012, GlaxoSmithKline pled guilty and paid $3 billion to resolve criminal and civil liability arising from the company’s unlawful prescription drug promotion, failure to report safety data, and false price reporting practices.

As a result of this recent litigation, many have questioned the FDA’s current role in regulation of off-label use and whether more or less intervention is needed. This debate sought to address these very issues.

Both Professors have written about FDA regulations. For example, Professor Epstein in his book, Overdose: How Excessive Government Regulation Stifles Pharmaceutical Innovation, and in an article in the Minnesota Law Review, “Against Permititis: Why Voluntary Organizations Should Regulate the Use of Cancer Drugs.” Professor Abbott has written about FDA regulations in the Iowa Law Review, Big Data and Pharmacovigilance: Using Health Information Exchanges to Revolutionize Drug Safety, and he has an article forthcoming with Ian Ayres at Yale Law School on Mechanisms for Regulating Off-Label Drug Use.

Art Caplan: #SaveJosh? Maybe, but What about the Rest?

Art Caplan has a new opinion piece up at MSNBC on the #SaveJosh social campaign that is seeking to get a young cancer patient access to an experimental drug under compassionate use policies. From the article:

If Josh were 67 instead of 7, he would already be out of luck. Those who are not very cute get less attention in their pursuit of unproven drugs. If Josh had parents who did not understand how to use social media, he would already be out of luck. If Josh did not have sharp, well-connected doctors, he would already be out of luck. But he is not in any of these categories, so he may yet get the drug.

All of which is to say, this is no way to handle requests from desperate patients, parents or families to try to save themselves or their loved ones from imminent death by giving them access to unproven, experimental drugs. We need an equitable compassionate use policy for everyone in this country.

Read the full article.

Clinical Trials of Primary Care Drugs: Could Smaller Be Better?

By Kate Greenwood

Cross-Posted at Heath Reform Watch

Lately it seems that each passing day brings another article about the cost of orphan drugs.  Earlier this week at FiercePharma, Tracy Staton reported that the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) has asked Alexion Pharmaceuticals to justify the price of its drug Soliris which is, per Staton, “the most expensive drug in the world” at around $569,000 a year.  Specifically, NICE seeks “‘clarification from the company on aspects of the manufacturing, research and development costs’” of the drug.  According to Staton, this latest development in a review process characterized by “halting progress” is “a departure from NICE’s usual calculations, which typically focus on quality-of-life years and the like.”

Pushback by NICE and other payers notwithstanding, the orphan drug market is growing.  As I blogged about here, in 2013 EvaluatePharma estimated that “the worldwide orphan drug market is set to grow to $127 [billion], a compound annual growth rate of +7.4% per year between 2012 and 2018[,]” which “is double that of the overall prescription drug market, excluding generics, which is set to grow at +3.7% per year.”  In a recent article in the New England Journal of Medicine, venture-capital investors Robert Kocher and Bryan Roberts note that “more than half of the 139 drugs approved by the FDA since 2009 are for orphan diseases” and suggest that there is a risk of “systematically underinvesting in other important areas of medicine.”

Kocher and Roberts’ explain that one reason that orphan drugs attract investment is that their development costs are low.  The problem or potential problem of underinvestment in diseases like depression and diabetes could therefore be addressed, they contend, by bringing the cost of developing treatments for these common conditions in line with the cost of developing treatments for rare diseases.  And, they argue, one promising approach to doing so is to reduce clinical trial costs by reducing the size of clinical trials. Read More

Review of Minssen, “Assessing the Inventiveness of Biopharmaceuticals under the European and U.S. Patent Laws”

Harold C. Wegner reviews Petrie-Flom Visiting Scholar Timo Minssen‘s doctoral thesis. From the review:
Patent applicants seeking to gain global patent protection beyond their home country borders need a better comparative knowledge of key elements of the patent laws of the several countries. Professor Timo Minssen in his superb doctoral thesis directly challenges the seemingly identical statutory and treaty standards for patentability in Europe and the United States in his comparative study of the laws of Europe and the United States with respect to the treaty standard of an “inventive step.” Timo Minssen, ASSESSING THE INVENTIVENESS OF BIOPHARMACEUTICALS UNDER THE EUROPEAN AND U.S. PATENT LAWS (Goteborg, Sweden: Ineko AB 2012). Professor Minssen’s doctoral thesis represents required reading for anyone seeking to unmask the subtle differences between American and European practice (emphasis added).
Read the full review.

Kevin Outterson on the Search for New Antibiotics

Kevin Outterson appeared on NPR’s “Here & Now” to discuss the growing problem of antibiotic resistance and possible ways to incentivize development of new antibiotics. From the interview:

On the misuse of antibiotics

“We should think of this as a global resource that needs to be conserved and taken care of. So antibiotics should never be used inappropriately. In the country right now, we have something on the order of 23 million people who are getting antibiotics for ear aches. Most of those situations would resolve on their own in a couple of days. We also give antibiotics many times for people just because they have some sort of a common cold — it’s estimated 18 million prescriptions a year — doesn’t help anyone who has the common cold. It’s a complete waste.”

On the rise of antibiotic-resistant bacteria

“It’s frightened people for more than a decade. You mentioned at the top the 23,000 Americans who are dying from resistant infections. The CDC said on top of that, there’s another 14,000 dying from a horrible disease, intestinal disease, called Clostridium difficile [C-diff] in the United States. Together, that’s larger than the number of people who die in this country each year from AIDS. And we’re not — as bad as things are now, the more troubling aspects, or what might happen in five or 10 years if some sort of a pathogen was resistant to everything we had got out to the population. It sounds like a Hollywood movie.”

You can listen to the full interview here.

Patent trolls/Monetizers/PAEs/NPEs and Bio/Pharma

By Nicholson Price

There’s recently been a lot of focus on patent trolls (so called by those who dislike them; they’re also known as patent assertion entities, nonpracticing entities, and monetizers, each with slightly different definitions; I describe them a bit more after the fold*): there have been Congressional hearings, a bill passed in the House, White House statements, state legislation, and quite a bit of academic attention.  Most attention, though, assumes this is mostly an issue for the high-tech and software industries; in particular, it’s usually assumed that the biotech and pharmaceutical industries are insulated from the phenomenon.  Robin Feldman (at UC Hastings) and I decided to reexamine that assumption, and argue in this piece that the conventional wisdom is wrong, and that biopharma is a relevant target for monetizers.

The basic argument of our piece is as follows: conventional wisdom holds that pharma need not worry about monetizers: even though patents are very important for drug companies, each drug is usually covered by just one or a few patents, and the company either owns them or has licensed them; otherwise it wouldn’t make the drug.  So there just aren’t patents out there that can be asserted; ergo, no monetizer problem.  And indeed, there hasn’t been much action so far.  We point to three challenges to this wisdom: (1) regulatory oversight increases the costs of inventing-around an asserted patent; (2) monetizers are spreading past low-hanging fruit; and (3) the business of selling drugs involves much more than just coming up with an active chemical compound, so that “much more” is still vulnerable to monetizers.  But the main thrust of the paper is against the assumption that there aren’t assertable patents out there.

We thought the patent holdings of universities would likely include lots of patents that might be used by monetizers against pharma, and we were right.  In a deliberately light skim across patent holdings of 5 major research university systems, we easily found many such patents.  The paper describes multiple different categories of patents that could be used, and provides examples of each.  We didn’t aim to be exhaustive, just to point out that the issue is a relevant one to biopharma (whatever you think of trolls), and that that industry should be taken into account–and should participate–in the policy debates about what happens next.  Read More

TOMORROW: Patents without Patents: Regulatory Incentives for Innovation in the Drug Industry

February 19, 2014 12:00 PM Wasserstein Hall 1015
1585 Massachusetts Ave., Cambridge

In the pharmaceutical industry, patents are the preeminent incentive for innovation in developing new drugs.  But patents aren’t the whole story; regulatory agencies also offer different forms of exclusivity—enforced by the agencies themselves—to encourage different forms of innovation in the industry.  This panel will discuss actual and potential roles for those rewards in the context of developing new drugs, new uses for old drugs, and new ways to make drugs, in both the United States and the European Union. Panelists include:

  • Benjamin N. Roin, Hieken Assistant Professor in Patent Law, Harvard Law School; Faculty Co-Director, the Petrie-Flom Center
  • W. Nicholson Price II, Academic Fellow, the Petrie-Flom Center
  • Timo Minssen, Associate Professor, University of Copenhagen Faculty of Law; Visiting Scholar, the Petrie-Flom Center
  • Moderator, Aaron Kesselheim, Assistant Professor of Medicine, Harvard Medical School; Director of the Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital

This event is free and open to the public. Lunch will be served. For questions, contact petrie-flom@law.harvard.edu or  617-495-2316.

 

More on drug quality: India

By Nicholson Price

The New York Times had a troubling piece this weekend about major problems in drug quality in India, where FDA Commissioner Margaret Hamburg is visiting to discuss safety issues. India makes 40% of the U.S.’s generic prescription and over-the-counter drugs.

Quality issues seem to be unfortunately common (though of course there are many top-quality manufacturers and plants as well).  Half of all the FDA’s drug-related warning letters last year were issued to Indian plants, and recently popular drugs (including Neurontin and Cipro) have been banned from the United States if they’re manufactured in India.  Part of the explanation is differing standards for different markets; manufacturing standards are higher for the U.S. than for India, but the same companies are doing the manufacturing, sometimes at the same plants. Problems aren’t just about quality control in the plants – there are also major concerns with fraud.  In a particularly harrowing situation, “One widely used antibiotic was found to contain no active ingredient after being randomly tested in a government lab. The test was kept secret for nearly a year while 100,000 useless pills continued to be dispensed.”

(If you’re interested in pharmaceutical counterfeiting and are in New England, there’s what promises to be a terrific conference on pharmaceutical counterfeiting at UNH School of Law in Concord, NH on February 19 and 20; details are here.) Read More