CardioBrief: Door Opens Wider for Off-Label Claims

— FDA decision called "horrible precedent"

MedicalToday

The FDA has finally reached a settlement in its long dispute with Amarin, manufacturer of the prescription fish oil product Vascepa. Last year a U.S. judge ruled against the FDA. The settlement brings an end to the litigation and will permit Amarin to promote off-label usage of Vascepa as long as its statements are "truthful and non-misleading."

The FDA downplays the larger significance of the settlement but many observers see the start of a major shift away from strict FDA regulation of drugs. "This is a horrible precedent," said Steve Nissen, MD, of the Cleveland Clinic. "Off-label promotion of drugs isn't about freedom of speech, it's about misleading physicians and patients about the benefits and risks of treatments. 'Truthful' promotion of icosapent ethyl [Vascepa] would require Amarin to state that the drug has no proven benefits in patients with moderately elevated triglycerides." (Nissen disclosed that he is chairing a large 13,000 patient trial with a different fish oil drug, Epanova.)

Currently, Vascepa is indicated only for use in people with extremely high triglycerides. Amarin had been frustrated by the FDA's repeated refusals to broaden the Vascepa label for the far larger population of patients with moderately elevated triglycerides. The effect of Vascepa in this population is now being studied in a large cardiovascular outcomes trial, REDUCE-IT.

In a Amarin said it will continue its "expanded promotion" of Vascepa which it initiated last summer following the judge's preliminary ruling. The Amarin case is a major test of FDA's ability to regulate speech in the wake of the , which was the first to grant sales representatives First Amendment protection for promotional speech about off-label uses.

Amarin acknowledged that the company "bears the responsibility of assuring that its communications to doctors regarding off-label use of Vascepa remain truthful and non-misleading." The settlement also allows for the company to consult with the FDA about new off-label claims. In addition, the settlement includes a dispute resolution provision to avoid future lawsuits, though future disputes between Amarin and the FDA would be resolved by the judge.

that the "proposed settlement order appears to reflect a broad concession by FDA that Caronia precludes the agency from pursuing criminal misbranding charges based solely on truthful, nonmisleading speech."

"The settlement doesn't create any legal precedent, but it certainly is part of a very worrying trend," said Amy Kapczynski, JD, director of the Global Health Justice Partnership at Yale. "The court here clearly didn't understand the role that the FDA plays in protecting the public, and in requiring companies to produce rigorous evidence about drugs. And the settlement certainly could embolden companies who would rather make their case about the truthfulness of their claims to a judge, instead of the FDA."

The FDA sought to downplay the significance of the settlement and to limit its implications. In a statement the FDA said that "the settlement is specific to this particular case and situation ... and does not signify a position on the First Amendment and commercial speech."

"The courts are at the precipice of taking over a fundamental FDA function of calling balls and strikes in the drug market about what's truthful and not misleading," Joshua Sharfstein, MD, of Johns Hopkins and a former deputy commissioner of the FDA, .