Irish drug company Amarin Pharma, Inc. (Amarin) and the U.S. Food and Drug Administration (FDA) agreed, on March 8, 2016, to settle claims that FDA regulations barring Amarin from making “truthful” and “non-misleading” statements about off-label uses for its omega-3 drug, Vascepa, violated Amarin’s right to engage in constitutionally protected speech. The underlying claims and settlement may have important implications for how drug makers market and sell their products going forward.

Case Timeline

In a complaint filed in the United States District Court for the Southern District of New York on July 7, 2015, Amarin and five internists preemptively sued FDA to obtain declaratory and injunctive relief, alleging that restrictions imposed by FDA regulations on the promotion of drugs for unapproved uses are invalid and unconstitutional under the First and Fifth Amendments to the Constitution. The gravamen of Plaintiffs’ First Amendment challenge was that the threat of prosecution for misbranding based on non-misleading speech to health care providers regarding an off-label use of an FDA-approved drug is constitutionally impermissible. Additionally, Plaintiffs alleged that FDA had violated their due process rights because it has not clarified what off-label promotion it considers lawful following the watershed decision of the Second Circuit Court of Appeals in United States v. Caronia, 703 F.3d 149 (2d Cir. 2012).  There, the Second Circuit held that the federal prohibition on drug misbranding must yield to the First Amendment and be construed “as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs” where the “off-label use is not prohibited.” Id. at 168-69.

FDA responded to the complaint, in part, by filing a letter to Amarin from June 5, 2015, stating that “FDA does not have concerns with much of the information [Amarin] proposed to communicate,” and that “FDA would not consider the dissemination of most of that information to be false or misleading, and . . . do[es] not intend to rely on it as evidence that Vascepa is intended for a use that would render Vascepa an unapproved new drug or misbranded.”

On August 7, 2015, the court granted Plaintiffs’ application for preliminary relief and declared that:

  1. “Amarin may engage in truthful and non-misleading speech promoting the off-label use of Vascepa, i.e., to treat patients with persistently high triglycerides, and under Caronia, such speech may not form the basis of a prosecution for misbranding”; and
  2. “the combination of statements and disclosures that Amarin proposes to make to doctors relating to the use of Vascepa to treat persons with persistently high triglycerides, as such communications have been modified herein, is truthful and non-misleading.”

On March 8, Amarin filed a proposed Stipulation and Order of Settlement, resolving its constitutional and other claims. The proposed settlement requires FDA to be bound by the determinations in Amarin Pharma and, further, to “contact Amarin with specific concerns or objections [regarding] proposed communications about the off-label use of Vascepa that Amarin has not yet communicated to doctors in promotion . . . .”  Amarin, meanwhile, must “assur[e] that its communications to doctors regarding off-label use of Vascepa remain truthful and non-misleading.”

The Outcome: Potential Implications

The outcome of Amarin Pharma by no means signals an end to litigation over restraints on off-label promotion.  In fact, a month after the August 7 ruling affirming Amarin’s free-speech and due process rights, another drug company, Pacira Pharmaceuticals, Inc. (“Pacira”), filed a federal lawsuit against FDA in response to a warning letter claiming that Pacira’s non-narcotic local analgesic, Exparel, was misbranded because Pacira had promoted it for “new uses for which it lack[ed] approval, and for which its labeling [did] not provide adequate directions for use”; namely, “postsurgical pain if used in surgical procedures other than bunionectomy and hemorrhoidectomy.” Similar to Amarin, Pacira alleged that “FDA also sought to preclude Pacira from making certain truthful and non-misleading statements about uses of Exparel” in violation of Pacira’s First and Fifth Amendment rights and the Administrative Procedure Act. Three months after Pacira brought suit, FDA settled Pacira’s claims, rescinded the Exparel warning letter, and approved a labeling supplement that “made certain changes to the Exparel label in order to clarify that its indication was not limited to bunionectomy and hemorrhoidectomy procedures.”

Key Takeaway

FDA’s resolution of Amarin’s and Pacira’s claims may generate other preemptive, “me too” litigation by pharmaceutical companies seeking to engage in truthful off-label promotion of drugs. The larger questions of when and how FDA and/or the Justice Department will file misbranding cases involving off-label promotion in light of Caronia remain largely unanswered.