A motion for a preliminary injunction in favor of Amarin Pharma Inc., barring the U.S. Food and Drug Administration (FDA) from blocking certain truthful and nonmisleading statements by Amarin about off-label uses of Vascepa®, its omega-3 drug. Amarin Pharma v. U.S. Food and Drug Administration, No. 15-3588 (S.D.N.Y., order entered August 7, 2015).The decision comes in the wake of the Second Circuit’s landmark ruling in United States v. Caronia, 703 F.3d 149 (2d Cir. 2012), in which the court overturned the conviction of a pharmaceutical sales representative who had promoted the off-label use of a drug using only truthful and non-misleading speech. In Caronia, the court of appeals ruled that, to avoid infringing First Amendment protections, “the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA [Federal Food, Drug, and Cosmetic Act] for speech promoting the lawful, off-label use of an FDA-approved drug.” To do so would impermissibly criminalize protected speech and violate First Amendment rights, the court held. FDA viewed the decision as a narrow one and indicated that it would continue its aggressive enforcement against off-label pharmaceutical drug promotion. And indeed it did, forcing settlements within months of the Caronia decision in misbranding/off-label actions against Amgen for $762 million and Par Pharmaceutical for $45 million.
In July 2012, FDA approved the use of Vascepa to treat adult patients with very high triglyceride levels (above 500mg/dL). Amarin later sought approval to market the drug for patients with persistently high triglyceride levels between 200 and 499 mg/dL. An FDA-approved study confirmed that the drug is effective in reducing such triglyceride levels, yet the FDA nonetheless rejected Amarin’s application for expanded approval because it was not clear that reduction of triglyceride levels alone would significantly reduce the risk for cardiovascular events in patients with persistently high triglyceride levels. FDA refused to authorize marketing of the drug for these patients until Amarin could show that the drug indeed reduced overall cardiovascular risk in patients. Nor was Amarin permitted to include the study results in the Vascepa label. In its letter to Amarin rejecting expanded use of Vascepa, FDA indicated that it would bring legal action if the company promoted the drug for use outside its approved bounds.
In May 2015, Amarin and a group of doctors filed a complaint against FDA seeking to lift the threat of legal action by raising a First Amendment challenge to the FDCA regulations that prohibited Amarin from disseminating truthful and non-misleading statements about Vascepa to health care professionals. Specifically, they argued that, according to the precedent set forth in Caronia, FDA does not have the authority to bring a misbranding action against a manufacturer based solely on truthful and non-misleading statements promoting an off-label use. FDA responded that it believed Caronia to be a fact-bound decision that hinged on the particular jury instructions and the government’s closing argument but did not broadly preclude misbranding actions, even if off-label promotion efforts consisted of truthful and non-misleading speech.
In a 69-page decision, U.S. District Judge Paul Engelmayer rejected FDA’s limited interpretation of Caronia, holding broadly “that the FDCA’s misbranding provisions cannot constitutionally criminalize, and therefore do not reach, the act of truthful and non-misleading speech promoting off-label use.” Therefore, the FDCA, “categorically, [does] not reach a manufacturer or its representative under those circumstances.” The court, however, cautioned that the First Amendment could not shield manufacturers or their representatives from false or misleading speech and that its protections were limited to expression, not conduct. And, while curtailing FDA’s ability to bring particular misbranding actions, it counseled that it would still be wise for manufacturers to consult with FDA before promoting off-label use, as it can be a fine line between misleading and non-misleading speech.
Future of Off-Label Promotion Enforcement
What is clear in the wake of the Amarin decision is perhaps little. Judge Engelmayer’s decision establishes that FDA cannot successfully bring misbranding actions against drug manufacturers or their representatives for truthful and non-misleading off-label drug promotion in the Southern District of New York, but it is unclear whether this analysis will gain traction outside Second Circuit courts. Even if this reasoning is adopted in other circuits, FDA will still retain the ability to bring off-label enforcement actions when the marketing is misleading or not demonstrably supported by scientific data. The focus will likely shift from asking if off-label uses were discussed with medical professionals to an inquiry about the specific language used in speaking with medical professionals. Accordingly, any company deciding proactively to market non-approved uses of a drug must take great care in determining the specific statements and marketing materials to be used and ensure that its representatives follow the vetted script. FDA has indicated that it would soon issue new guidelines for off-label promotion but no timetable has yet been established. At a minimum, Amarin and Caronia will certainly change the manner in which individuals and companies may defend themselves if they are the subject of an investigation for off-label marketing.
This Drug and Device Bulletin is a collaboration between the Shook, Hardy & Bacon Government and Regulatory team and the Pharmaceutical and Medical Device practice. Read more Drug & Device news >>