Federal court ruling upsets FDA's regulation of off-label promotion

On Aug. 7, US District Judge Paul Engelmayer granted a preliminary injunction to Amarin Pharma, proscribing FDA from filing a “misbranding” action against Amarin, should it provide “truthful and non-misleading” information to physicians promoting the off-label use of its approved drug, Vascepa (icosapent ethyl, derived from fish oil) for patients with persistently high triglycerides. The closely watched case presents a dramatic and significant threat to FDA’s existing framework for policing off-label promotion—and activity for which, in recent years, companies ranging from GlaxoSmithKline to Abbott Labs to Allergan, among others, have paid billions in fines.

A background: Under the Food Drug and Cosmetic Act of 1938, pharma companies much show that their products are safe; and under a 1962 law, must also show that they are effective. At the same time, it has been a longstanding principle that physicians can legally prescribe any approved product for just about any condition; in fact, upwards of 20% of all prescriptions are for off-label uses, and even higher percentages for pediatric medications and antipsychotics. The dilemma that FDA has tried to address over the years is how to control non-approved uses without interfering with physicians’ ability to prescribe. An elaborate dance of providing “truthful, non-misleading” information but not “promotional” information has evolved. In Amarin’s case, FDA conceded that clinical trials for the expanded use of its drug had meaningful data, but decided not to approve the drug, resulting in Amarin’s suit.

In his ruling (Case 1:15-cv-03588-PAE, in the Eastern District of Southern New York), Engelmayer followed closely from an earlier trial, United States v Caronia, in which the conviction of a sales rep for performing off-label promotion was overruled. The basic counterargument was a matter of First Amendment rights of “commercial speech.” In his ruling, Engelmayer writes that “FDA argues that that protecting truthful speech aimed at promoting off-label drug use is “a frontal assault . . . on the framework for new drug approval that Congress created in 1962,” because allowing a manufacturer to promote such use “has to the potential to eviscerate [the] FDA drug approval regime.” The short answer is that the FDCA’s drug-approval framework predates modern First Amendment law respecting commercial speech.” That “modern” interpretation, in part, is based on recent case law that establishes protections for commercial speech. (Interestingly, one of the citations is the Sorrell case, in which marketers of prescription data took action against the attorney general of Vermont, who sought to prevent the dissemination of these data)

As of Aug. 10, FDA had not responded to the Aug. 7 Engelmayer ruling. Both that case, and the earlier Caronia case, could get elevated to higher courts in time. Meanwhile, a likely first effect is to slow down if not stop FDA litigation against pharma companies for off-label promotion, which has resulted in billions of dollars of fines in recent years against GSK, Abbott and others. And it could energize pharma marketing efforts for promoting off-label applications (and the result of that could be a reduction in performing clinical trials for extended uses, as FDA fears).

The judge also noted that “Although the FDA cannot require a manufacturer to choreograph its truthful promotional speech to conform to the agency’s specifications, there is practical wisdom to much of the FDA’s guidance, including that a manufacturer vet and script in advance its statements about a drug’s off-label use. A manufacturer that leaves its sales force at liberty to converse unscripted with doctors about off-label use of an approved drug invites a misbranding action if false or misleading (e.g., one-sided or incomplete) representations result.”