Article: November 2015: Life Sciences Litigation Update

Amarin Wins Injunction Against FDA over Off-Label Marketing. Historically, FDA-approved drug products have only been promoted for their expressly approved uses. On August 7, 2015, the Southern District of New York granted Amarin Pharma, Inc.’s application for preliminary relief to engage in truthful and non-misleading speech relating to off-label use of its Vascepa drug product, free from the threat of an FDA misbranding action. Amarin Pharma, Inc., v. U.S. Food & Drug Admin., No. 15-3588 (S.D.N.Y. Aug. 7, 2015). The court held that a misbranding action could not be based on truthful promotional speech alone. The significance of this decision is that it potentially opens the door for pharmaceutical companies to start promoting their drug products for uses that have not been approved by the FDA (“off-label uses.”)

Vascepa, composed of pure eicosapentaenoic acid (“EPA”), an omega-3 fatty acid, is approved by the FDA for treating adult patients with triglyceride levels above 500 mg/dL of blood. Id. at 20. Amarin also sought FDA approval to market Vascepa to treat patients with triglyceride levels between 200 and 499 mg/dL who are already on statin therapy, but the FDA refused to approve this indication until Amarin conducted an additional study to demonstrate that Vascepa can reduce cardiovascular risk in this patient population, in addition to lowering triglyceride levels. Id. at 20-21. The FDA had previously determined that Vascepa is safe, and the results of an earlier FDA-approved study (the ANCHOR study) indicate that Vascepa is also effective in reducing triglyceride levels in the new patient population. Id. at 20. While the results of the study regarding cardiovascular risk are pending, however, the FDA warned Amarin that including information regarding the ANCHOR study in Vascepa’s labeling may be considered misbranding under the Food Drug and Cosmetic Act (“FDCA”). Id. at 26.

In response to this warning, Amarin brought a “First Amendment challenge to FDA regulations that prohibit Amarin ‘from making completely truthful and non-misleading statements about its product to sophisticated healthcare professionals.’” Id. at 26. Under the FDCA, the FDA requires manufacturers to demonstrate the safety and efficacy of their pharmaceuticals before they are approved. Id. at 4. The promotion of an approved product for unapproved uses is not allowed by the FDA, which considers the promotion of an off-label use to be criminal “misbranding” under 21 U.S.C. § 331(a). Id. at 9. The FDA, however, does not regulate doctors. Once a drug has been approved by the FDA, physicians may prescribe the drug for FDA-approved uses as well as unapproved, off-label uses. Id. at 5. In fact, the Court cited a 2001 study that found that 21% of prescriptions in the United States were off label. Id.

Amarin sought an injunction prohibiting the FDA from bringing a misbranding action for promoting Vascepa for its unapproved use or, in the alternative, a declaration that its intended communications were protected against misbranding actions. Id. at 31. In response, the FDA agreed that the content of some of Amarin’s intended statements were permissible, but objected to the content of others entirely. Id. at 31-35. The FDA also sought to restrict the manner in which Amarin could disseminate any of the information. Id.

The Southern District of New York based its decision to grant preliminary relief on the Second Circuit’s 2012 decision in U.S. v. Caronia, 703 F.3d 149 (2d Cir. 2012). Id. at 43-53. In Caronia, a sales representative who had been caught promoting the drug Xyrem to doctors for unapproved uses was convicted of conspiracy to misbrand. Id. at 17-18. The Second Circuit reversed the conviction, holding that the First Amendment protects the truthful promotion of FDA-approved drugs for off-label uses. Id. at 18. Specifically, the Second Circuit held that “the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug.” Id. (quoting Caronia, 703 F.3d at 169). The Amarin court held that, under Caronia, the FDA may not bring an action for misbranding based on truthful promotional speech alone. Id. at 45.

On its face, the Amarin decision appears to open the door to the promotion of off-label uses of approved drug products, but several aspects of the decision must be considered in looking forward to determine how widespread off-label promotion may become.

Amarin only limits the FDA’s ability to bring misbranding actions based on truthful promotional speech alone. Indeed, Judge Engelmeyer specifically highlighted two forms of off-label marketing that are not protected by the First Amendment. Id. at 52-53. First, the FDA may still prosecute manufacturers that engage in false or misleading speech, which the First Amendment does not protect. Second, the First Amendment protects expression, but not conduct. Thus, non-communicative activities, such as payments to physicians, are not protected, and in such situations, the FDA may use truthful promotional speech to prove that non-communicative activities have been used to improperly promote off-label use. Thus, drug manufacturers must remain vigilant regarding the statements and actions of their representatives.

It also remains to be seen how broadly Amarin’s holding will be applied by the courts and by the FDA. While Amarin limits the FDA’s ability to prove misbranding, the decision does not require the FDA to approve off-label promotional materials. Similar to FDA’s response to Amarin’s proposed promotional statements, Judge Engelmeyer only approved a specific set of promotional statements, even editing certain statements himself. It will take time for the FDA and the industry to gain clarity regarding the scope of “truthful promotional speech.” This may open the door, however, for pharmaceutical companies to begin engaging in promotion of their drug products for non-FDA approved uses. Such promotion would represent a large change in the way that drugs are promoted in this country.

Finally, Judge Engelmeyer makes clear that statements that are truthful today may not be truthful in the future. Pharmaceutical manufacturers engaging in off-label promotional speech, particularly statements that have not been approved by the FDA, will need to be particularly vigilant to ensure that their promotional materials contain accurate information reflecting the most current data. Every statement not approved by the FDA increases a pharmaceutical manufacturer’s exposure.