Federal Court Grants Requested Injunction in Amarin: Confirms Caronia Stands for Proposition that “the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label us of an FDA-approved drug.”

In an eagerly-anticipated the decision, On August 7, 2015, Judge Paul A. Engelmayer of the Southern District of New York granted Amarin Pharma Inc.’s request for a preliminary injunction barring the FDA from pursuing misbranding actions against Amarin based on truthful, non-misleading statements about off-label use of the triglyceride-lowering drug Vascepa. The decision, Amarin Pharma, Inc. v. United States Food and Drug Administration, No. 15 Civ 3588 (PAE) (August 7, 2015), rest squarely on the foundation of the Second Circuit’s decision in United States v. Caronia, 703 F.3d 149 (2d Cir. 2012), and rejects FDA’s efforts to restrict the holding or import of the earlier Second Circuit decision.

To state the dispute in brief, Vascepa is approved for treating patients at risk of heart disease with very high triglyceride levels also being treated with statins. Amarin wanted to promote the drug for use in patients treated with statins with high but not very high triglyceride levels, a common existing off-label use. A study of Amarin’s efficacy in that population had met its FDA-approved end-points, but in the interim between approval and completion of the study FDA changed its position on appropriate measures of efficacy. With appropriate disclaimers, Amarin wanted to call attention to the results of that study and other evidence, with the statement that “supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.”

When FDA made it clear that it would consider such communications evidence of misbranding, Amarin brought suit alleging that the statements were truthful non-misleading speech, which the Second Circuit, in Caronia, had found could not form the basis of a misbranding action under the Food, Drug and Cosmetic Act (FDCA) because interpreting the act to prohibit this conduct would violate the First Amendment. Following a practice it had used in other cases, FDA sought to moot judicial review through use of a June 5, 2015 letter representing that it would not consider certain statements evidence of misbranding if Amarin abided by certain restrictions and conditions. FDA, however, declined to make any such representation with respect to the “supportive but not conclusive research” statement.

In a clearly worded rebuke of FDA’s efforts to limit Caronia to the facts of that case, the Court made clear that Caronia meant what it said: “the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label us of an FDA-approved drug.” Caronia, 703 F.3d at 168-69. The court found that the FDA’s June 5th letter had not mooted the case and controversy before the court, slip op. at 42, noting that Amarin had never agreed to – and was not required to agree to – FDA’s proposed restrictions limiting communications on the use at issue to, inter alia, communications initiated by doctors, communications in “scientific” settings and communications not made by sales staff, noting that the reasons given in Caronia “apply across the board to all truthful and non-misleading promotional speech.” Slip op. at 51. It further rejected the complex “speech as evidence of intent” statutory rationale advanced by FDA for exempting regulation of off-label promotion from First Amendment scrutiny, observing that since “the FDCA’s drug approval framework predates modern First Amendment law respecting commercial speech …the provisions of a 1962 statute that implicate such speech, such as the FDA’s misbranding provisions, today must be considered, and to the extent ambiguous construed, in light of contemporary First Amendment law, under which truthful and non-misleading commercial speech is constitutionally protected, subject to the Central Hudson framework.” Slip op. at 49.

Applying that standard, while the court found that preserving the integrity of the FDA’s drug approval process and reducing patient exposure to ineffective drugs were substantial interests, these interests were not directly advanced by restricting truthful off-label promotion. Factors the court considered in reaching this conclusion were the legality of the use itself and the availability of numerous less speech-restrictive alternatives to advance the interests identified by FDA. Slip op. at 48. It then engaged in a detailed analysis of Amarin’s proposed statements and disclaimers and found that, with minor revisions to clarify the status and limitations of certain research, the statements were non-misleading. It therefore entered an injunction barring FDA from considering these communications as evidence of misbranding. Interestingly, the court specifically rejected FDA’s argument that a “substantial but not conclusive” claim that would be permissible under the standards applicable to dietary supplements would be sufficiently potentially misleading to ban in the context of drugs. In rejecting FDA’s argument that only communications supported by “significant scientific agreement” should be permitted with respect to prescription medications, the court discounted FDA’s suggestions that doctors are incapable of processing the significance of the distinction between these two measures of evidential support. Slip op. at 62-63.

In entering the injunction, the Amarin court was careful to make clear that the First Amendment was not an absolute shield to misbranding prosecutions arising out of off-label promotion, as false or misleading statements about off-label sue would remain actionable. It also noted that non-communicative promotional activities, such as awarding free trips to doctors as a reward for using a product off-label, would also remain actionable. Furthermore, while pointing out that there was no legal restrictions to unscripted communications by detail representatives with doctors about off-label use, prudence might counsel common-sense voluntary restrictions and/or advance consultation with FDA, as FDA remains free to act against false or misleading one-sided or incomplete statements. Slip op. at 53. It should be noted, however, the court’s detailed analysis of the proposed disclosures and rejection of certain additional disclosures requested by FDA suggests that something less than absolute clarity and comprehensive disclosure is necessary to avoid speech being deemed misleading.

It should be kept in mind that the opinion is merely a decision on an application for a preliminary injunction, and even reduced to a final judgment would be subject to appeal. As a well-reasoned decision giving prospective application to Caronia and specifically authorizing communications about an off-label use, however, the decision represents a milestone in using the First Amendment to limit the FDA’s restrictions on off-label promotion.