On March 8, 2016, Amarin Pharma, Inc. and FDA entered into a formal settlement, close to a year after the U.S. District Court for the Southern District of New York granted a preliminary injunction against FDA’s threats to treat Amarin’s proposed truthful and non-misleading off-label marketing about its drug, Vascepa (icosapent ethyl), as violative of the Food, Drug, and Cosmetic Act (“FDCA”). In August of last year, the Court ruled that FDA was impermissibly chilling truthful speech in violation of the First Amendment. Amarin Pharma, Inc. v. FDA, 2015 U.S. Dist. LEXIS 103944 (S.D. N.Y. Aug. 7, 2015). The parties’ settlement now accepts the court’s decision, reflecting a fundamental change in FDA’s previous policy of effectively prohibiting any off-label marketing by prescription drug and medical device companies, regardless of whether the proposed speech was objectively truthful.

The settlement comes after a series of high-profile losses for FDA and the DOJ in the government’s attempt to prohibit and criminalize truthful off-label marketing. The first significant loss came in 2012, when the U.S. Court of Appeals for Second Circuit reversed a conviction against a pharmaceutical salesperson (Alfred Caronia) for off-labeling marketing as violative of the First Amendment because his speech was not alleged to have been false or misleading.  United States v. Caronia, 703 F.3d 149 (2^nd Cir. 2012). And late last year, FDA settled with Pacira Pharmaceuticals a lawsuit brought against the Agency on First Amendment grounds.  Most recently, last week a federal jury in Texas acquitted a medical device company and the company’s CEO, in charges that included misbranding a device with off-label promotional campaign – a prosecution failure that may have finally pushed FDA’s hand in a months-long negotiation with Amarin.

Back in August 2015, Judge Paul A. Engelmayer of the U.S. District Court for the Southern District of New York granted a preliminary injunction against FDA and in favor of Amarin regarding the company’s ability to make truthful, non-misleading statements promoting Vascepa, which had undergone clinical trials and been approved by FDA for treating adults with high triglyceride levels above 500 mg/dL.  However, Amarin wanted to promote Vascepa for treating adults with triglyceride levels between 200 and 499 mg/dL.  This was an off-label use for which FDA had not approved the drug although certain clinical data supported the efficacy of that off-label use, as we’ve previously described.  When FDA threatened to bring a misbranding action based on Amarin’s stated intentions to promote the drug’s off-label use, Amarin filed suit seeking a preliminary injunction against FDA, asserting that FDA’s threat chilled its First Amendment right to engage in truthful, non-misleading speech.  The Court agreed, entered a preliminary injunction against FDA, and then directed the parties “to confer…as to the future course of and next steps in the case, and submit a joint letter…setting forth the parties’ views on the subject.”  Thereafter the case was stayed.  In December 2015, the parties informed the court that they “have engaged in and continue to engage in settlement discussions in the hopes of resolving this case” and requested that the stay be extended.

This week’s settlement agreement stipulates that “Amarin may engage in truthful and non-misleading speech promoting the off-label use of Vascepa…and such speech may not form the basis of a prosecution for misbranding.” However, Amarin “bears the responsibility, going forward, of assuring that its communications to doctors regarding off-label use of Vascepa remain truthful and non-misleading.” To this end, the agreement also provides a special procedure through 2020 in which FDA will give Amarin advance review for as many as two promotional communications annually about off-label uses of Vascepa. Moreover, the agreement establishes a specific process for resolving any concerns that FDA voices about those communications prior to the parties returning to court.

Now that FDA has publicly recognized that, consistent with First Amendment principles, it cannot suppress or attempt to criminalize truthful and non-misleading speech under the FDCA, the broader question remains of how the Agency is going to determine whether off-label marketing is “misleading,” in its view, under the Act.  It seems likely that the settlement will now prompt FDA to provide regulations and/or guidance for industry on the factors it will consider in reviewing off-label marketing. Indeed, the Agency’s chief counsel publicly stated around a year ago that a stakeholder meeting on off-label marketing policies was being planned for 2015. Whether or not such a meeting takes place this year, 2016 is shaping up to be a transformative one for members of both FDA and regulated industry who grapple with the often-blurry lines between on-label vs. off-label promotion, not to mention truthful vs. misleading statements, in a complex medical world.