By Elta Mariani
In Amarin Pharma, Inc. v. FDA (“Amarin”), the United States District Court for the Southern District of New York (the “Court”) ruled that truthful, non-misleading promotion of a drug approved by the U.S. Food and Drug Administration (“FDA”) for non-FDA approved (“off-label”) use is protected under the First Amendment of the Constitution. As long as this speech remains truthful and non-misleading, it cannot be “chilled” with threats including that of a misbranding action under the Federal Food, Drug and Cosmetic Act (“FDCA”). The Court reached this decision by interpreting predecessor case United States v. Caronia, 703 F.3d 149 (2d Cir. 2012) broadly and engaged in re-writing of Amarin Pharma, Inc. (“Amarin”) proposed statements to ensure they were truthful and non-misleading. While Amarin’s request for preliminary relief from criminal action under the FDCA was granted, its claim for preliminary relief from civil action under the False Claims Act was deemed not yet ripe.
This case was brought by biopharmaceutical company Amarin Pharma, Inc. (“Amarin”) and multiple physicians for preliminary relief on First Amendment, and alternatively due process, grounds. Amarin’s drug Vascepa is FDA-approved for the treatment of patients with very high blood triglyceride levels (“severe hypertriglyceridemia”). Comprised of the omega-3 fatty acid “pure eicosapentaenoic acid,” Vasepa is considered safe for use by such patients. The issue in this case arose when Amarin sought to make truthful statements to doctors regarding an off-label use of Vascepa, but feared FDA prosecution on FDCA misbranding charges.
FDA regulation of pharmaceuticals dates back to 1938, when Congress first enacted the FDCA. In 1962, Congress amended the FDCA to required manufacturers to demonstrate that their products are safe and effective for their intended use prior to distribution, and gave approval power to the FDA (which established pre-clinical and clinical trial requirements towards this end). On its face, the FDCA prohibits misbranding (punishable by fines and imprisonment), not off-label promotion of drugs, but the FDA has interpreted the FDCA prohibition on misbranding to include off-label promotion. Recent FDA actions show an increased interest in bringing mislabeling charges under this interpretation of the FDCA, and the result has been large settlements (e.g., the 2012 GlaxoSmithKline guilty plea in the District of Massachusetts involving a $1 billion fine).
Amarin was the culmination of Amarin’s efforts to approve and market Vascepa for an additional, off-label use for patients on statin therapy with high (as opposed to very high) triglyceride blood levels. On July 6, 2009, it entered into a written, special protocol assessment (“SPA”) agreement with the FDA. Such an agreement guarantees FDA approval if certain size and design parameters are met. In this study, Vascepa also had to sufficiently reduce triglyceride levels for patients with high triglyceride blood levels on statin therapy. The resulting ANCHOR study met these parameters and benchmarks for effectiveness.
SPA guidance indicates that the FDA will only break an SPA agreement if “a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after testing has begun.” The FDA claimed this condition was met and rescinded the SPA agreement for this secondary use of Vascepa, pointing to various other studies with different drugs that indicated an unclear link between lowering triglyceride levels and reduced cardiovascular risk.
After appealing the decision through three FDA review levels and receiving guidance from the FDA indicating that it would pursue mislabeling charges if Amarin tried to promote the off-label use tested in the ANCHOR study, Amarin filed an action for relief on May 7, 2015. The two main ways Amarin desired to promote the off-label use were 1) distribution of ANCHOR results, and 2) additional reports supporting the correlation between lowering triglyceride levels and reduced cardiovascular risk. After much back-and-forth, the two sides were unable agree on language satisfactory to both.
The Court analyzed the communications between the parties and determined that Amarin met the requirements for preliminary relief because 1) it is likely to succeed on the merits, 2) it is likely to suffer irreparable harm absent preliminary relief, 3) the balance of equities tips in its favor, and 4) preliminary relief is in the public interest. First, reading predecessor case Caronia broadly and beyond its specific facts, the Court deemed Amarin likely to succeed on the merits because its statements are truthful and non-misleading promotion of off-label use. Any language the Court believed not truthful or misleading, it redrafted. The Court next determined that the FDA’s misbranding action threat was enough of a specific present objective harm or threat to establish a claim for irreparable harm. The Court addressed the last two elements together, and determined that the public interest favored granting Amarin relief because of the importance of preserving First Amendment rights. The FDA’s concerns that relief would undermine the drug approval process and endanger the public health were dismissed as having no basis.
In Amarin, the FDA offered three counterarguments that were all rejected by the Court in turn. The first FDA argument, that protecting truthful speech to promote off-label drug use was an attack on Congress’s new drug approval framework, was dismissed as contrary to contemporary First Amendment interpretation. The second FDA contention, that only certain types of truthful and non-misleading manufacturer statements about off-label use deserved protection, was met with the observation that Caronia did not limit its holding to certain types of speech. Finally, the third FDA argument, that Caronia did not preclude it from using statements as evidence to prove intent or motive in a criminal misbranding action, was deemed irrelevant in this situation, where the act itself is legal and the speech is true.
In response to the FDA’s concerns, the Court noted three limitations on commercial speech promoting off-label drug use. False or misleading speech is not protected, false or misleading conduct is not protected, and finally, the subjective nature of “false or misleading” plus the developing nature of science and medicine will likely guarantee pharmaceutical consultation with the FDA regarding statements promoting off-label use. The Court also determined that going forward, Amarin carries the burden of ensuring that new studies and data do not change the (as now modified) truthful and non-misleading nature of its statements.
Amarin is noteworthy because its ruling, consistent with Caronia, provides momentum to the Caronia court’s pro-pharmaceutical company ruling involving the First Amendment. As both rulings come from district courts, they do not have tremendous precedential weight, but they could represent a new court trend nationwide in such cases. The arguments used by both parties, the tests and standards used in the Court’s analysis, and the Court’s comfort with stepping in and literally rewriting statements intended to be shared with physicians are in some ways unprecedented, and potentially prophetic.
Additionally, Amarin’s claim for preliminary relief from civil action under the False Claims Act was deemed not yet ripe. This leaves open another avenue for FDA action that has yet to be addressed and is worth watching. If Amarin could face civil penalties, its “win” in Amarin (protection from criminal action for misbranding) would be bittersweet.
Finally, this case like any other must be read in the greater national regulatory and political context. As drug prices have increased, pushing pharmaceutical companies into the spotlight for seemingly opportunist behavior in their acquisitions and other business practices, government scrutiny, from not only the FDA but also Congress, has increased. Rulings like Amarin and Caronia do not seem to support recent government attempts to reign in pharmaceuticals, and the Amarin court’s dicta about extant limitations on pharmaceutical company statements may not be sufficient. Demands of non-price sensitive consumers for the latest and best medicine could encourage profit-focused pharmaceutical company behavior despite these limitations. Thus, court rulings protecting pharmaceutical company speech and relying on such limitations may actually undermine government regulatory efforts. With the unsure fate of the Affordable Care Act and the delay of its special taxes on pharmaceutical companies, this in-flux area of law continues to be prescient and watch-worthy.
Elta Mariani is a 3L student at Boston College Law. During law school, she has served as a president of the student-run Health Law Society, and worked at athenahealth, Tufts Medical Center, and the law firm of Donoghue, Barrett & Singal. She received her undergraduate degree from Cornell University.
 The Court did not address this alternative ground for relief.
 U.S. Food and Drug Admin., Guidance for Industry: Special Protocol Assessment (2002), at 10, http://www.fda.gov/
 In Caronia, the Court of Appeals for the Second Circuit reversed a pharmaceutical salesman’s conviction for making truthful statements about off-label use of a drug to physicians. Determining that FDA had prosecuted the salesman for his speech alone, and applying the principle of constitutional avoidance, the court narrowly construed the FDCA provisions regarding illegal misbranding. Pharmaceutical marketing speech was determined protected expression under the First Amendment in the context of promoting off-label use when it passes the Central Hudson four-prong test for constitutionally protected commercial speech and promotes a lawful, off-label use of an FDA-approved drug.