Amarin Pharma and the FDA recently announced a widely expected settlement of First Amendment litigation over restrictions on the company’s promotion of its Vascepa product.
Readers may recall that this was one of several recent challenges to the FDA’s attempt to restrict off-label promotion of prescription products, even if that speech is truthful and not misleading. Several trends have combined to undercut this overreach by FDA. A pharmaceutical representative’s promotion of an FDA-approved drug’s off-label use is speech. And “speech in aid of pharmaceutical marketing … is a form of expression protected by the Free Speech Clause of the First Amendment.” Sorrell v. IMS Health, Inc., 131 S.Ct. 2653, 2659 (2011). Then, in United States v. Caronia, 703 F.3d 149 (2d Cir. 2012), the court vacated a conviction for conspiracy to sell a misbranded drug, recognizing that to criminalize the simple promotion of a drug’s off-label use by pharmaceutical manufacturers would run afoul of the First Amendment. Off-label drug usage is not unlawful, and the FDA’s drug approval process generally contemplates that approved drugs will be used in off-label ways. So, it does not follow that prohibiting the truthful promotion of off-label drug usage would directly further the government’s stated goals of preserving the efficacy of FDA’s drug approval process and reducing patient exposure to unsafe and ineffective drugs. This ruling was not limited to a subset of truthful promotional speech, such as statements responding to doctors’ queries or statements by non-sales personnel.
In Amarin Pharma, Inc. v. FDA, No. 1:15-cv-03588 (S.D.N.Y. Aug. 7, 2015), the issues surrounded proposed statements by the company concerning its Vascepa®, an omega-3 fatty acid, approved in 2012 as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia. The FDA had entered into an SPA (Special Protocol Assessment) with the company for an expanded use. Amarin believed it had satisfied all of FDA’s requirements to obtain approval of Vascepa® for persistently high triglycerides pursuant to the SPA. But FDA warned that any effort by Amarin to market Vascepa® for the proposed supplemental use could constitute misbranding under FDCA.
The company sued, arguing that the threat of prosecution for misbranding has a chilling effect on commercial speech protected by the First Amendment. It sought an injunction prohibiting the FDA from bringing a misbranding action for Amarin’s truthful and non-misleading statements regarding Vascepa® directly to healthcare professionals—not in direct-to-consumer advertising. Specifically the company wanted to affirm its right to disseminate study results; report supportive but not conclusive research shows that their product may reduce the risk of coronary heart disease; and distribute reprints of peer-reviewed scientific publications relevant to the reduction of the risk of coronary heart disease. The company was willing to do this along with “contemporaneous disclosures” to ensure that the messages Amarin communicated to doctors concerning the use of Vascepa® in patients with persistently high triglycerides was not misleading. The FDA did not agree, and attempted to distinguish Caronia as fact-bound, turning on the particular jury instructions given in that trial.
Judge Paul A. Engelmayer rejected FDA’s interpretation of Caronia: the FDA may not bring such an action based on truthful promotional speech alone, consistent with the First Amendment. Misbranding is not analogous to speech crimes of jury tampering, blackmail, or insider trading. “Where the speech at issue consists of truthful and non-misleading speech promoting the off-label use of an FDA-approved drug, such speech, under Caronia, cannot be the act upon which an action for misbranding is based.”
The court then evaluated and ruled on each of Amarin’s proposed off-label statements concerning Vascepa® along with FDA’s responses. The “agreed-upon statements and disclosures” (e.g., statements concerning the results of the key study; statements, along with the proposed contemporaneous disclosures) were “based on current information, truthful and non-misleading.”
The “contested disclosures” such as “not-approved for” language were handled through a court-crafted, revised disclosure. The proposed cardiovascular disease claim, as revised during litigation, given its qualified phrasing and its acceptance elsewhere by the FDA, was found by the court to be presently truthful and non-misleading.
The court did mention some caveats: A manufacturer that leaves its sales force at liberty to communicate unscripted with doctors about off-label use of an approved drug invites a misbranding action if false or misleading (e.g., one-sided or incomplete) representations result. Caronia leaves the FDA free to act against such lapses. The dynamic nature of science and medicine is that knowledge is ever-advancing. A statement that is fair and balanced today may become incomplete or otherwise misleading in the future as new studies are done and new data is acquired. So, said the court, Amarin bears the responsibility, going forward, of assuring that its communications to doctors regarding off-label use of Vascepa® remain truthful and non-misleading.
Rather than appeal, the government worked towards a settlement. Under its terms, the FDA agrees to be bound by the court’s conclusion that Amarin may engage in truthful and nonmisleading speech promoting the off-label use of the drug. The company committed t ensure that it stays current on evolving science and updates its promotional statements accordingly. The settlement agreement also provides for a procedure by which the FDA will give advance review to as many as two promotional communications annually for off-label uses of Vascepa, along with a timetable and process for resolving any concerns that the FDA may have about those new communications.
A copy of the settlement here.