The latest development in the simmering war over off-label drug promotion came on March 8, when Amarin Pharma reached a proposed settlement with the FDA that would allow the company to market its cardiovascular drug, Vascepa, for certain unapproved uses. While the settlement must be approved by the district court, it already has fueled speculation about ever-broader challenges to off-label restrictions. The unique set of facts at issue in Amarin, however, likely will limit the ability of other pharmaceutical companies to follow suit, at least in the short term.
Amarin sued the FDA in May 2015, relying on the Second Circuit’s 2012 opinion in United States v. Caronia, which held that the Food, Drug and Cosmetic Act did not prohibit a pharmaceutical sales representative’s truthful statements about off-label use of his company’s drug, Xyrem. Procedurally, the Amarin dispute was unusual. Vascepa was approved in 2011 for the treatment of patients with very high triglyceride levels. Before the approval, Amarin entered into a special protocol assessment (SPA) with the FDA under which Vascepa would be studied (the ANCHOR study) in patients with slightly lower triglyceride levels, with the expectation of additional approval if the drug met study benchmarks. In 2013, Amarin filed for such approval.
Subsequent to the SPA, however, studies of other cardiovascular products suggested that reducing triglyceride levels in high-risk patients did not lead to real clinical benefits for patients in terms of reducing events such as heart attack and stroke. An FDA Advisory Committee found “substantial uncertainty” as to whether Vascepa would reduce such real-life risks, and the agency rescinded the SPA. While acknowledging that the drug had met the ANCHOR study goals, the agency refused to approve the new indication until a second study confirmed Vascepa was able to reduce major cardiac events in such patients. The FDA refused to allow Amarin to add the ANCHOR study results to Vascepa’s label, and warned that the drug might be misbranded if marketed for the new use.
Amarin filed suit in the Southern District of New York, seeking permission to engage in truthful and non-misleading off-label promotion of Vascepa, to make statements based on the ANCHOR study results, and to provide physicians with copies of the study and other peer-reviewed publications. The company offered to include disclaimers acknowledging that the use was not approved by the FDA and that another clinical study was underway. The FDA responded by offering to permit some of the proposed statements if accompanied by more detailed disclosures written by the agency itself, but refused to allow any statements about the drug’s ability to reduce the risk of coronary artery disease – despite the fact that similar omega-3 food and dietary supplements were allowed to make those claims. Not surprisingly, the company refused.
On August 7, 2015, the district court ruled in Amarin’s favor, granting the company permission to “engage in truthful and non-misleading speech promoting the off-label use of Vascepa” and prohibiting that speech from being used as the basis for a misbranding prosecution. Interpreting Caronia to bar misbranding actions based on truthful promotional speech alone – and concluding that the company’s proposed statements, with minor changes, were indeed truthful – the district court rejected the FDA’s arguments. Settlement discussions soon followed.
In many ways, Amarin was the worst possible challenge for the FDA to take up. By filing in the Southern District of New York, which is bound by Second Circuit precedent, Amarin precluded the district court from revisiting Caronia’s underlying First Amendment analysis (even had the judge been so inclined). While the FDA tried to distinguish the Caronia facts, if anything the facts of Amarin were even clearer: the company did exactly what the FDA requested in carrying out the ANCHOR study, and the agency acknowledged that most of what the company sought to say was true. The agency even went so far as to offer to let the company make the same claims if it repackaged the product as an OTC supplement rather than a prescription drug. Bound by clear legal precedent, and with the FDA acknowledging the truth of the company’s claims, it would have been nearly impossible for the district court to find in the government’s favor — and equally unrealistic to expect the Second Circuit to reverse the decision if the government sought to appeal. Whether the same will hold true in circuits not bound by Caronia, or in cases where the FDA challenges the truth of the company’s scientific claims (and has not reneged on any promises to the company), remains to be seen.