Monday Morning Recap: The Week (8.11.14-8.17.14) in Drug & Device Law & Policy

August 19, 2014 by · Leave a Comment
Filed under: Monday Morning Recap 

Picture3The student’s are back here at Seton Hall Law and the Tuesday Monday Morning Recap is too, after a restful but all-too-brief vacation. Monday Morning Recap is the post where we call out the drug and device law and policy developments that caught our eye and made us think over the previous week.  You can see all of our previous Monday Morning Recap posts here.

1. The high-priced Hepatitis C drug Sovaldi continued to make headlines this past week. At Forbes, Yevginiy Feldman noted that “the UK’s National Institute for Health and Care Excellence (NICE) just approved the drug as being cost-effective, and recommended it for subgroups of patients.” Feldman suggests that, “given that a system with very tight price controls, and what can be described as a true single-payer system, decided to cover Sovaldi for some subgroup of patients, perhaps the mud-slinging against [Sovaldi's manufacturer] Gilead is a bit unwarranted. The evidence appears to be shifting in Sovaldi’s favor.

2. At Kaiser Health News, Jim Burress reported on the barriers that stand in the way of more widespread use of the anti-viral medication Truvada by individuals at risk of, but who do not have, HIV or AIDS. Burress quotes researcher Dr. Melanie Thompson who “says no doctor would refuse to prescribe cholesterol-lowering statins to patients because they’re overweight.  Somehow, the conversation around PrEP is different. ‘So I think it’s a very interesting moralistic attitude that soon will be outdated.  But I do think that this is a barrier for some patients,’ Thompson says. ‘They feel stigmatized. And honestly, health care providers need to step up their game and do better than that.‘”

3. AP Health Writer Matthew Perrone wrote about former AIDS activist Gregg Gonsalves, who “still travels to Washington, but with a different agenda: to defend the FDA.”  Perrone reports that “[s]ince May, three states – Colorado, Louisiana and Missouri – have passed laws designed to allow terminally ill patients to receive experimental drugs that have not been cleared by the FDA. Arizona will vote on its own so-called ‘right to try’ initiative in November and lawmakers in Florida, Oklahoma and Utah are set to introduce similar bills. All of these efforts are driven by lobbyists from the Goldwater Institute, a libertarian think tank. … In closing his talk on Capitol Hill earlier this summer, Gonsalves warned Senate staffers that a political shift to the right in coming elections could ‘change the game’ for drug safety and effectiveness. ‘We will have a different FDA than we have had for the last 30 years.’”

4. Charles Ornstein of Pro Publica broke the news that “[n]ext month, when the federal government releases data about payments to physicians from pharmaceutical and medical device makers, one-third of the records will be withheld because of data inconsistencies, an official told ProPublica. The issue is the latest hurdle for the federal government as it seeks to launch the already-delayed Open Payments database mandated under the Physician Payment Sunshine Act, a provision of the 2010 Affordable Care Act.” The data inconsistencies were uncovered after a physician in Kentucky named David E. Mann complained that some of the payments attributed to him were actually made to a David E. Mann in Florida. Even before he discovered the inconsistencies, Dr. Mann was frustrated. On August 1st, he Tweeted the following: “Just completed the application to view my #sunshine act data on CMS website. Applying for a visa to North Korea would be simpler.

5. Finally, at the Drug and Device Law blog, Jim Beck opines, with his usual entertaining irascibility, about the Alabama Supreme Court’s “re-decision” in Weeks v. Wyeth. In Weeks II, the Court held, as it did the first time around in Weeks I, that a plaintiff who was injured by a generic drug could bring suit against the manufacturer of the drug’s branded equivalent, to the extent that the plaintiff’s physician prescribed the generic drug in reliance on misrepresentations made by the branded manufacturer. Beck’s “[b]ottom line”: “Alabama has more home-grown plaintiff lawyers than pharmaceutical companies – and after Weeks II, it most assuredly always will.” (A video of (among other things) me giving my (contrary) take on Weeks I and innovator liability generally is here.)

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Ebola Outbreak Shines a Light on Compassionate Use

coleman_carl_lg2The Ebola outbreak, which has claimed nearly 1,000 lives since its emergence in West Africa in December 2013, has brought renewed attention to policies surrounding the “compassionate use” of unapproved medications – i.e., the provision of unapproved medications to individuals outside the context of clinical trials.   The issue rose to the forefront early last week when it was reported that two American aid workers in Liberia were treated with an “experimental drug that has never before been tested for safety in humans.”  Both workers appeared to respond well to the drug, known as ZMapp.  The drug was also provided to a Spanish priest, who died shortly thereafter; it was unclear whether he took the drug before he died.  Following some controversy over the fact that the first three recipients of the drug were all foreign aid workers, on Tuesday it was reported that the drug’s manufacturer had sent its remaining stocks of the drug to Liberia for the treatment of two African doctors.

The FDA recognizes three broad categories of compassionate use, which are grouped under the general label of “expanded access.”  These include expanded access for individual patients, including for emergency use; expanded access for intermediate-size patient populations; and expanded access for large patient populations under a treatment IND or treatment protocol.  All of these categories are limited to patients who have serious or immediately life-threatening diseases or conditions for which no comparable or satisfactory alternative treatment exists.  The FDA must determine that the potential benefits of the unapproved drug outweigh the potential risks, and that the risks “are not unreasonable in the context of the disease or condition to be treated.”  In addition, the FDA must determine that allowing expanded access “will not interfere with the initiation, conduct or completion of clinical investigations that could support marketing approval of the expanded access use or otherwise compromise the potential development of the expanded access use.”

The FDA typically grants most requests for expanded access.  When requests are denied, they most frequently involve emergency requests to use drugs that are not already undergoing clinical trials – precisely the situation facing ZMapp.  On the one hand, it is understandable that the FDA would be cautious in allowing expanded access when no safety information exists and when there is no time to perform an exhaustive assessment.   On the other hand, patients who are expected to die in a short time because they have no treatment alternatives may reasonably decide that they are willing to assume a high level of risk.  Moreover, if clinical trials have not even been initiated, allowing expanded access cannot possibly interfere with the trials’ completion.  While there is some possibility that systematically allowing expanded access in emergency situations would interfere with the initiation of trials, the manufacturer would have its own incentives to initiate trials once the expected demand for the drug is sufficiently high.

For now, all of these questions are moot, as existing supplies of ZMapp have reportedly been exhausted.   When more supplies become available, further requests for expanded access are certain to arise.  However, granting access to the drug through compassionate use programs is not a long-term solution.  As an ethics panel convened by the World Health Organization concluded on Tuesday, the ideal way to introduce new Ebola medications is “in the best possible clinical trials under the circumstances in order to definitely prove their safety and efficacy or provide evidence to stop their utilization.”

Clinical trials of Ebola treatment will of course raise difficult questions in their own right.  Unlike with expanded access, where everyone obtains the medication they have expressly requested, in a clinical trial some participants may be assigned to control groups that receive different medications or even placebos.  Because no effective treatment for Ebola currently exists, placebo-controlled trials of new Ebola treatments would appear to be consistent with the ethical principles in the Declaration of Helsinki.  Yet, particularly after American and Spanish foreign aid workers received the first doses of the experimental medications through compassionate use programs, asking African patients to enroll in placebo-controlled trials would surely be controversial.  As the WHO panel delicately put it, the goal should be to devise “ethical ways to gather data while striving to provide optimal care under the prevailing circumstances.”   The challenge will be to figure out effective strategies for carrying this out.

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REMS As A New Competitive Sword?

paradiseLGjpg_1The pharmaceutical industry has long-been criticized for use of anticompetitive tactics.  Brand pharmaceutical companies have been publicly accused of several high-profile activities to increase profits and stifle competition.  These include: shifting demand to a modified form of an existing brand drug (often called “product hopping”), using authorized generics to retain market share, frivolously filing citizens petitions to delay generic market entry, and using reverse payment settlements to keep generics of the market during their 180 day exclusivity period (otherwise known as pay-for-delay settlements).  A persistent opponent in these tactics, the Federal Trade Commission (FTC), routinely invokes antitrust and unfair competition law to frame legal challenges.  In fact, the 2012 Supreme Court case FTC v. Actavis examined pay-for-delay settlements entered into between new drug application (NDA) patent holders and generic applicants, holding that they were not per se illegal but subject to a rule of reason test.

Many are now pointing to brand pharmaceutical manufacturers use of Risk Evaluation and Mitigation Strategies (REMS) as the latest anticompetitive tactic.  The Food and Drug Administration Amendments Act of 2007 (FDAAA) introduced REMS to enhance the FDA’s post-approval authority over drugs.  FDAAA contains new statutory provisions that allow the FDA to require further studies for safety and efficacy, along with increased authority for FDA to review these commitments on a continuing basis.  The FDA can require a REMS as either a condition of approval or, in the case of already approved products, as a subsequent additional condition for continued marketing.  A REMS may require a medication guide for patients, prescription physician information, communications to health care providers and pharmacies, limitations on labeling, promotion, and prescribing in order to assure safe use by patients, and a plan for implementation.  Violations trigger civil money penalties and subject manufacturers to litigation under misbranding provisions within the Food, Drug and Cosmetic Act.  To date, the FDA has implemented 70 REMS, half of which include elements to assure safe use (ETASU) that often take the form of distribution restrictions, training and recordkeeping requirements for prescribers and pharmacists, and prescribing limitations.

As noted here, a recent study announced last month estimates that $5.4 billion per year has been lost in prescription drug savings due to distribution restrictions imposed by brand drug manufacturers.  Brand manufacturers subject to a REMS for an NDA drug product claim that they cannot make samples of that drug available to the generic applicant because they would be in violation of distribution restrictions placed on the products by the FDA in the REMS.  However, in order to obtain approval through the generic drug approval process, a generic applicant must show bioequivalence to the NDA product through pharmacokinetic and pharmacodynamic measures.  The medical community is already targeting this practice as problematic, noting that it is a direct threat to the effective use of a drug-safety tool in order to increase profits and keep generic products off the market. In an April 2014 New England Journal of Medicine article, excerpted here, the authors urge that “the use of REMS requirements to block the market entry of generic drugs could well lead to higher health care costs and adverse patient outcomes.”

The REMS tactic is playing out in court in New Jersey.  Mylan Pharmaceuticals filed a complaint earlier this year against Celgene Corporation, claiming violations of federal antitrust law.  Mylan alleges that Celgene refuses to distribute the products Thalomid and Revlimid for bioequivalence testing for products in development by Mylan.  Because of their teratogenic nature, the FDA has invoked ETASU REMS for both Thalomid and Revlimid consisting of various extensive requirements to prevent embryo-fetal exposure, among other things: see here and here.  One aspect of the ETASU is strong oversight and requirements for distribution only through authorized dispensing pharmacies.  Celgene’s position is that the distribution restrictions prohibit the transfer of drug samples to Mylan for any purpose, including bioequivalence studies.

The FTC has taken a strong interest in the case, and filed an amicus brief on June 17, 2014.  In the brief, the FTC argues that Celgene is potentially engaging in exclusionary conduct in violation of the Sherman Act by “refusing to sell to rivals.”  The FTC notes that Celgene may be in violation of both Section 1 and  2 of the Sherman Act by not only refusing to directly provide samples to Mylan, but also implementing restrictions that prevent Mylan from purchasing samples though customary distribution channels.  Celgene has moved to dismiss.

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Monday Morning Recap: The Week (7.28.14-8.3.14) in Drug & Device Law & Policy

Picture3Here’s this week’s Monday Morning Recap, the post where we call out the drug and device law and policy developments that caught our eye and made us think over the previous week.  You can see all of our previous Monday Morning Recap posts here.

1. This past week, Julie Steenhuysen at Reuters filed a report on “[t]he worst Ebola outbreak in history[.]” The outbreak “is heaping new pressure on U.S. regulators to speed the development of treatments for the deadly virus, which has killed more than 700 people since February. The U.S. Food and Drug Administration on Friday said in an emailed statement the agency ‘stands ready’ to work with companies and investigators working with patients ‘in dire need of treatment.’ . . . FDA’s statement follow calls by doctors fed up by the lack of progress on Ebola treatments, a market deemed too small to gain much attention by large pharmaceutical companies. Earlier this month, the agency put a hold on a Tekmira Pharmaceuticals Corp clinical trial of TKM-Ebola, one of the few Ebola treatments advanced enough to be tested in people. The hold prompted a North Carolina physician with family members in West Africa to say enough. ‘This should be the last Ebola epidemic without a cure,’ said Dr. Ahmed Tejan-Sie, an internist from Burlington.”

2. The FDA announced that it was “notifying Congress of its intention to publish a proposed risk-based oversight framework for laboratory developed tests (LDTs), which are designed, manufactured and used within a single laboratory.” Andrew Pollack at the New York Times explains: “Test systems or kits that are sold to hospitals, laboratories, doctor’s offices and the public have long been regulated as medical devices, giving the agency the opportunity to review them before they are marketed. But tests developed and performed by a single laboratory, with all samples being sent there, have typically not been. The F.D.A. had claimed the legal authority to regulate these so-called laboratory-developed tests, but said it was exercising ‘enforcement discretion’ not to do so. The agency said on Thursday that such discretion must end because circumstances had changed. Lab-developed tests once were fairly simple, often developed by a hospital for tests on its own patients. Now the tests can be complex and are being developed by companies and marketed widely.”

3. Also this past week, BioMarin Pharmaceutical announced that it had sold its rare pediatric disease priority review voucher to Regeneron Pharmaceuticals for $67.5 million. BioMarin was awarded the voucher in February “when it received approval of VIMIZIM®, a new biological product for patients with Mucopolysaccharidosis type IVA, also known as Morquio A syndrome.” Per Ron Winslow and Joseph Walker at the Wall Street Journal: “The voucher was the first to be issued under the pediatric incentive program, and also the first to change hands.” For additional background, see my post here.

4. At Pharmalot, Peter Loftus reported that a group of medical societies and pharmaceutical industry trade groups has written a letter to the Centers for Medicare & Medicaid Services (CMS) expressing concern that when the first Physician Payments Sunshine Act report is released later this month it will not provide the context needed to allow the public to understand the reasons for payments made by drug and device companies to physicians. CMS, Loftus writes, responded that it “does plan to make available the nature of payment for each payment or transfer of value made to a physician or teaching hospital and will also include context on the website.”

5. Finally, at CommonHealth blog Deborah Becker discusses a newly-released report from The New England Comparative Effectiveness Public Advisory Council that “contains some surprising findings about medication maintenance addiction treatment. It says that methadone, long used to treat heroin addiction, may be the most effective and cheapest treatment. The report . . . found that when comparing methadone with suboxone (Buprenorphine) or naltrexone (Vivitrol), more patients stayed in treatment longer if they were taking methadone. In follow-ups with patients three to 12 months after they first started taking medication, 63 percent of methadone patients were still in treatment, compared with 52 percent of those taking suboxone and 28 percent on naltrexone. Methadone also appears to be the cheapest maintenance medication, despite the requirement of having a health care facility daily distribute the drug to patients.”

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Monday Morning Recap: The Previous Week (7.21.14-7.27.14) in Drug & Device Law & Policy

July 28, 2014 by · 1 Comment
Filed under: Drugs & Devices, Monday Morning Recap 

Picture3Here’s this week’s Monday Morning Recap, the post where we call out the drug and device law and policy developments that caught our eye and made us think over the previous week.  You can see all of our previous Monday Morning Recap posts here.

1. Last Wednesday, two advocacy groups, the Medicare Rights Center and Social Security Works, released a report calling on Congress to take four concrete steps to reduce the price Medicare pays for prescription drugs: (1) restore the rebates that were lost with the passage of the Medicare Modernization Act; (2) allow Medicare to negotiate drug prices on behalf of Part D enrollees by establishing “Medicare-administered drug plans, with a uniform premium and a vetted benefit design to ensure safety, appropriate use and high value care”; (3) speed up the closure of the Medicare “doughnut hole” by securing additional discounts from drug manufacturers, and (4) “[p]romote cost-effective prescribing for Part B prescription drugs”, which are typically administered in a doctor’s office by injection or infusion, and which tend to be very expensive.

2. As we noted here, concerns have been raised about manufacturers’ use of Risk Evaluation and Mitigation Strategies (REMS) to delay entry of generic drugs. This week the Generic Pharmaceutical Association released a commissioned study that attempts to quantify the impact. The author writes: “This paper estimates lost savings on forty generic small-molecule products whose market entry, according to a survey of generic drug manufacturers, is currently delayed by misuse of REMS or other restricted access programs. Specifically, this paper identifies $5.4 billion in annual pharmaceutical spending that could be saved if generic versions of the forty identified drugs were allowed to come to market.

3. The Second Circuit decided an important case this week involving the Food and Drug Administration’s (lack of) response to the use of antibiotics to help farm animals grow. At Bill of Health, Diana Winters writes: “This issue has enormous public health consequences, but the consequences of this case extend beyond antibiotic use, to agency practice in general.  The opinion sanctions egregious agency delay and a tremendous lacuna in decision making.

4. Reuters reported on a new partnership between Britain’s Medical Research Council and seven leading drug manufacturers, under which academic researchers “will gain access to ‘deprioritized’ pharmaceutical compounds. Often these compounds have been dropped from development because they are not sufficiently effective against a particular condition, but they may still be useful against other diseases with shared biological pathways. . . . While drugmakers have traditionally been reluctant to share their compounds, there is a growing recognition that outside experts may be able to unlock value by taking a different approach, resulting in shared profits between companies and academic institutions.”

5. Finally, I recommend the series of posts Richard Cassin published at The FCPA Blog last week (here, here, and here) on the ways in which in-house lawyers, including in-house lawyers at drug and device companies, are “caught between their duty as advocates on the one hand, and the modern concept of ethics and compliance on the other hand.”

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