The FDA has long treated off-label marketing – the promotion of drugs for uses that have not received FDA approval – as evidence of intent to violate the “misbranding” provisions of the Food, Drug and Cosmetic Act (“FDCA”), 21 U.S.C. § 301 et seq.

According to the FDA, pharmaceutical manufacturers and their representatives may not engage in off-label marketing of their drug products, even though physicians are free to prescribe drugs for non-approved uses, and scientists are free to publish papers regarding research into unapproved indications. On this basis, the Department of Justice has successfully brought at least dozens of off-label marketing suits and recovered billions of dollars in penalties and settlements from individuals and corporations. See non-comprehensive list of off-label promotion pharmaceutical settlements here.

The Caronia Effect

For this reason, many observers saw the December 2012 decision in United States v. Caronia, 703 F.3d 149 (2d Cir. 2012) by a divided Second Circuit panel as signaling a potential sea of change in the law governing off-label promotion of drugs. In Caronia, the court overturned the criminal conviction of a pharmaceutical sales representative found guilty of conspiring to promote the off-label use of Xyrem, a drug marketed by Orphan Medical.


Although Xyrem is approved for the treatment of adult narcolepsy with cataplexy, Caronia had provided physicians with clinical evidence demonstrating Xyrem’s efficacy in patients suffering from fibromyalgia, restless leg syndrome and Parkinson’s disease. In throwing out the conviction, 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.” 703 F.3d at 169.

According to the Caronia majority, convicting the representative for off-label marketing that was truthful and not misleading could impinge the representative’s First Amendment rights, requiring a narrow construction of the relevant statutes and regulations. Applying the analytical framework applicable to commercial speech established by the Supreme Court in Cent. Hudson Gas & Elec. Corp. v. Pub. Serv. Comm’n of N.Y., 447 U.S. 557, 563–64, (1980), the Court concluded that “government’s construction of the FDCA’s misbranding provisions does not directly advance its interest in reducing patient exposure to off-label drugs or in preserving the efficacy of the FDA drug approval process because the off-label use of such drugs continues to be generally lawful.” 703 F.3d at 167. It also held that “construction of the FDCA to impose a complete and criminal ban on off-label promotion by pharmaceutical manufacturers is more extensive than necessary to achieve the government’s substantial interests” in, e.g., “reducing patient exposure to unsafe, untested drugs and maintaining the integrity of the FDA-approval process.” Id. at 167-68.

The FDA did not appeal this decision, but interpreted the Second Circuit’s ruling narrowly, stating that it “d[id] not believe that the Caronia decision will significantly affect the agency’s enforcement” of the FDCA’s misbranding provisions. Indeed, in the two-and-a-half years that followed Caronia, few if any pharmaceutical companies sought to assert First Amendment defenses in FDA enforcement actions against off-label marketing. Some suggest that this is because corporations are not well-situated to assert a First Amendment defense in a case against the Justice Department with potentially dire consequences in the event of failure. See e.g., Caronia and the First Amendment Defense to Off-Label Marketing: A Six Month Re-Assessment.

Amarin’s Challenge

This changed last month, when drug maker Amarin filed suit against the FDA, asking the United States District Court for the Southern District of New York to hold that the FDA’s prohibitions on off-label promotion as applied to “speech Amarin proposes to make and [doctors] wish to receive” about its approved prescription medication Vascepa® “are unconstitutional, and to declare that Amarin may engage in that speech.”

Vascepa is drug containing a purified ester of EPA derived from fish oil, that the FDA approved “for use as an adjunct to diet to reduce triglyceride levels in adult patients with very high triglycerides.” The FDA recently refused to extend Vascepa’s approval for use in reducing trigylcerides in patients with persistently high triglycerides, notwithstanding the results of a randomized, double-blind, placebo-controlled clinical study demonstrating that Vascepa reduces triglycerides (and has other favorable effects) in such patients.


According to Amarin’s complaint, “[a]lthough doctors regularly prescribe Vascepa for off-label uses, including to treat patients with persistently high triglycerides, FDA regulations forbid Amarin from promoting Vascepa for any off-label use without risk of criminal prosecution under the Food, Drug, and Cosmetic Act [ ] and civil liability under the False Claims Act [ ], even if the information conveyed is truthful and non-misleading.” Amarin also points out that the FDA allows makers of dietary supplements containing EPA and DHA ingredients to make the “qualified health claim” 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.

Amarin further alleges that its sales representatives nevertheless would be prosecuted for misbranding if they made the same statement about Vascepa.

Now, in an unusual move that appears intended to head-off the lawsuit, the FDA has written a letter to Amarin stating that the marketing materials the drug maker proposes to distribute to doctors would not concern the FDA. The June 5, 2015 letter signed by Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, states that under the circumstances presented, the FDA would not object to Amarin’s dissemination of clinical trial results related to unapproved uses of Vascepa, nor consider their distribution to be evidence of “intended use.”

The FDA further stated that while it might consider the inclusion of a qualified health claim in connection with the distribution of Vascepa “misleading or as evidence of an intent to market the product for an unapproved use,” it offered that Amarin “could make such a claim in connection with the distribution of [its] product if [it] were to repackage and re-label it as a dietary supplement.” The FDA also reminded Amarin that it is “currently engaged in a comprehensive review of its regulations and guidance documents regarding manufacturer’s dissemination of information regarding their medical products, and new guidance will be forthcoming.” Notably, the FDA announced its intent to engage in this review in June 2014, and has provided no timetable for providing such guidance, which in any event will be technically nonbinding.


The FDA has the challenging task of balancing the legitimate interests of the public to be protected from unwarranted and false claims from drug manufacturers regarding their products with the equally legitimate rights of drug companies to freely communicate with the public about those drug products. While the freedoms guaranteed by the First Amendment have boundaries, they are also robust and it is appropriate for courts to scrutinize government sanctions for speech. While there certainly may be instances where the FDA could narrowly tailor its regulations limiting off-label promotions to fulfill the compelling interest of protecting the public from unsafe or ineffective medicines, there is also the very real concern over government restraint of truthful speech based on its content.

The Caronia Court found that the FDA’s construction of its misbranding provisions to prohibit truthful and non-misleading commercial speech about a lawful activity (off-label use) cannot withstand First Amendment scrutiny. Indeed, the FDA’s position on off-label marketing has created the puzzling situation where nearly anyone can talk about the safety and efficacy of a drug’s off-label use, except for the manufacturer – often the entity likely to have the most information about that drug. As a result of the FDA’s insistence that the Caronia decision would not significantly affect the agency’s enforcement activities, many commentators have speculated that the FDA will try to settle any suit or claim that could result in a decision that erodes its authority to regulate off-label marketing. The FDA’s June 5, 2015 letter to Amarin thus may have been motivated by a desire to avoid judicial examination of this thorny issue.

In these circumstances, it is reasonable to question whether a blanket prohibition of all off-label marketing can withstand the judicial scrutiny of a First Amendment challenge even outside of the Second Circuit.  On the other hand, it is also very possible that individual cases may present unique and compelling interests that warrant FDA intervention and a reasonable limitation on a company’s commercial speech.  It is therefore logical to presume that drug companies will not rush en masse to pursue unbridled off-label promotional activities, while the FDA in turn is unlikely to take a “business as usual” approach in dealing with alleged off-label marketing.

Nevertheless, if the FDA’s reaction to the Amarin suit is any indication of its future strategy, we may see less government reliance on off-label marketing litigation as a means of regulating drug promotion. At the same time, recent Supreme Court and appellate decisions holding that FDA laws do not preempt or preclude private litigation could presage a shift toward private sector lawsuits playing a more significant role in shaping drug advertising.