August 13, 2015
In a pointed and thoughtful repudiation of FDA’s longstanding policy, the U.S. District Court for the Southern District of New York held on August 7, 2015, that the First Amendment precludes the prohibition and criminalization of truthful, non-misleading off-label speech under the Federal Food, Drug, and Cosmetic Act ("FDCA"). Amarin Pharma, Inc. v. U.S. Food & Drug Admin., No. 1:15-cv-03588-PAE (S.D.N.Y. Aug. 7, 2015). Applying the Second Circuit’s seminal 2012 decision in United States v. Caronia, 703 F.3d 149 (2d Cir. 2012), the Amarin court granted a motion for preliminary injunction to permit Amarin’s proactive off-label promotion of an approved drug. In reaching this conclusion, the court delved into Amarin’s proposed off-label product claims and disclosures and concluded that the specific statements were truthful and non-misleading based on currently available information.
Amarin offers critical traction for challenges to off-label promotion enforcement and prosecutions. Indeed, the court roundly rejected FDA’s attempts "to marginalize the holding" in Caronia "as fact-bound." Slip op. at 47. The Amarin court’s "considered and firm view" was that FDA may not bring a misbranding action based on truthful promotional speech alone. Id. at 45.
Amarin is the manufacturer of the approved drug Vascepa, an ethyl ester of an omega-3 fatty acid that was developed to improve cardiovascular health. Amarin initially sought FDA approval for two separate uses of Vascepa. FDA approved Amarin’s application to market Vascepa for treating adult patients with very high triglyceride levels, while denying approval of the use in adult patients with slightly lower triglyceride levels who were already on statin therapy (i.e., those with "persistently high triglyceride levels"). Id at 20. Although it was undisputed that the drug effectively reduces triglyceride levels–and that the drug is safe–FDA rejected the application because studies were "unclear [as to] whether reducing the triglyceride levels of persons with persistently high triglycerides reduces cardiovascular risk." Id. at 21. Thereafter, FDA warned that it might consider Vascepa misbranded if Amarin marketed it for "persistently high triglyceride levels" without approval. Id. at 26.
Seeking to preempt such a misbranding action, Amarin brought an as-applied First Amendment challenge to FDA regulations that prevented it "’from making completely truthful and non-misleading statements about its product to sophisticated healthcare professionals.’" Id. at 26 (quoting Amarin complaint). In its complaint, Amarin set forth the proposed statements and disclosures it intended to make regarding the off-label use of Vascepa. Id. at 29-30. Amarin moved for a preliminary injunction barring FDA from bringing a misbranding action against Amarin for its truthful and non-misleading statements to doctors regarding Vascepa; Amarin also asked for a declaratory judgment that its intended statements were shielded from misbranding enforcement actions. Id. at 31.
In response to Amarin’s complaint, the Director of FDA’s Center for Drug Evaluation and Research ("CDER"), Dr. Janet Woodcock, sent Amarin a letter acknowledging that some of the statements "fall within the scope" of existing FDA guidance. Id. In particular, FDA noted that Amarin could (1) communicate clinical trial results regarding off-label uses of Vascepa pursuant to existing guidance that delineates acceptable methods to distribute journal articles concerning unapproved uses and (2) respond to unsolicited requests for off-label information. FDA also set out conditions and told Amarin that, if it met those conditions, FDA would agree not to bring a misbranding action. Id. at 32. Amarin agreed with certain FDA suggestions set forth in the Woodcock letter, but disputed others.
In the August 7 opinion, the district court concluded that a genuine case or controversy existed because FDA expressly threatened to bring a misbranding action against Amarin for promoting Vascepa off-label and Amarin rejected several of FDA’s proposed conditions on the company’s dissemination of information relating to the off-label uses. Id. at 40-42. This threat, the court reasoned, had a chilling effect on Amarin’s exercise of its First Amendment rights. Id. Rather than mooting the controversy at hand, the Woodcock letter "sharpened for Amarin the circumstances under which FDA reserved the right to bring a misbranding action." Id. at 42.
Turning to the request for a preliminary injunction–and applying Caronia–the court concluded that the First Amendment bars FDA from pursuing a misbranding action where the targeted actus reus is "truthful and non-misleading speech promoting the off-label use of an FDA-approved drug." Id. at 49. The Amarin court disagreed with FDA’s analogies to the crimes of jury tampering, blackmail, and insider trading in which "the speech is the act." Id. "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." Id. (emphasis in original).
Notably, the court went so far as to analyze whether Amarin’s proposed communications were truthful and non-misleading. The court explained that "Vascepa’s unusual and extensive regulatory history ma[de] it realistic to determine, at this early stage, the truthfulness of Amarin’s proposed statements regarding [the] off-label use." Id. at 54. In particular, Amarin sought to disseminate (1) reprints of 13 peer-reviewed scientific publications, (2) a statement and chart summarizing a key study regarding Vascepa’s efficacy in reducing triglyceride levels, and (3) several statements and disclosures. After dispensing with the reprints and study summary and chart, as well as several statements that FDA did not seriously contest, the court analyzed two contested disclosures and suggested appropriate language to ensure that these disclosures conveyed a truthful and non-misleading message. Id. at 57-61. Where the parties’ conflicting proposals resulted in a "close question" about a particular statement, the court "err[ed] on the side of caution, meaning in favor of giving doctors more, not less, information." Id. at 61.
In granting the preliminary injunction, the court determined that Amarin faced irreparable harm because its First Amendment rights would be chilled. Further, the court held that the balance of equities and the public interest were both overwhelmingly in favor of granting relief because of the effect that FDA’s threat to pursue an enforcement action had on Amarin’s First Amendment rights and the apparent lack of any danger to public health posed by the proposed communications. Id. at 66-68.
Following the groundbreaking opinion by the Second Circuit in Caronia, life science companies routinely invoked the First Amendment–and Caronia‘s reasoning–as a defense to allegations targeting off-label promotion. Meanwhile, the government has insisted that Caronia is limited to its particular facts and jurisdiction, and negotiated resolutions of off-label prosecutions and False Claims Act investigations have continued apace.
Amarin offers fresh ammunition to companies confronting off-label allegations to rebut any contention that Caronia was an outlier. The opinion emphasizes that Caronia‘s holding is "a definitive one of statutory construction," which explicitly "’decline[s] to adopt the government’s construction of the FDCA’s misbranding provisions’" to prohibit truthful off-label speech. Id. at 48 (quoting Caronia, 703 F.3d at 168-69). Moreover, the opinion further erodes the purported policy rationale and statutory interpretation underlying FDA’s off-label restrictions. The Amarin court was unswayed by FDA’s assertion that the proposed off-label communications by Amarin represented a "’frontal assault . . . on the framework for new drug approval that Congress created in 1962.’" Id. at 35. Indeed, the court observed that "[h]ad the FDA believed that Caronia gravely undermined the drug approval process, it should have sought review of that decision." Id. at 67.
Amarin also sets forth several important caveats that clarify the limits on claims that off-label promotion is protected under the First Amendment. First, the court noted that, "Caronia does not limit the Government’s ability to use promotional speech to establish intent in a misbranding action with a proper actus reus." Id. at 52. For example, the court explained, truthful speech could be evidence of intent to promote off-label use when a manufacturer also "paid doctors money or bought them resort vacations." Id. In such circumstances, the Amarin court suggested, the government could bring a misbranding action based on the actus reus of the payments. In addition, the court highlighted that the First Amendment does not protect false or misleading commercial speech and that it protects expression, not conduct. Thus, "[a] manufacturer that engages in non-communicative activities to promote off-label use cannot use the First Amendment as a shield." Id.
The court also offered advice for manufacturers. Although FDA "cannot require a manufacturer to choreograph its truthful promotional speech to conform to the agency’s specifications," the court urged manufacturers to heed the "practical wisdom" contained in "much of the FDA guidance, including that a manufacturer vet and script in advance its statements about a drug’s off-label use" and consider consulting with FDA before promoting off-label use. Id. at 53. The court cautioned that companies have a continuing responsibility to ensure that their communications remain truthful and non-misleading: "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." Id. at 66.
For decades, FDA has stood firm on its view that off-label promotion violates the FDCA. Despite token gestures toward free speech–e.g., guidance on the distribution of scientific and medical publications–FDA’s stance has shifted only negligibly in the past decade. Although Caronia and Amarin are unlikely to compel swift, significant change–and the reach of those cases is formally limited to courts within the Second Circuit–it is clear that the pressure on FDA is mounting. As FDA considers new guidance that it has promised to issue in the near future regarding off-label promotion, Amarin should ensure that First Amendment considerations will remain in the forefront. In the meantime, as Amarin progresses toward a potential appeal, other life sciences companies like Amarin will surely push the courts to follow the trail blazed by the courts of the Second Circuit.
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