On August 7, Citing the First Amendment, a Southern District of New York court ruled that FDA cannot limit a manufacturer’s “truthful and non-misleading speech promoting off-label use” of a drug and evaluated specific statements and disclosures that the manufacturer planned to make, determining certain communications as modified by the Court were truthful and non-misleading. Amarin, joined by four physician-plaintiffs, filed suit against FDA, following FDA’s refusal to permit certain truthful off-label statements and disclosures of Vascepa® (isosapent ethyl) with FDA’s permission to permit only certain statements with additional disclosure language.
Vascepa is manufactured by Amarin Pharma, Inc., an Irish biopharmaceutical company focused on cardiovascular health. Vascepa, Amarin’s first FDA-approved product, has approved indications for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (triglyceride levels of 500 mg/dL of blood or above). Despite this label limitation, Amarin claims that physicians have been consistently prescribing Vascepa to reduce triglyceride levels in patients who have persistently high, but not severely high triglyceride levels. Under FDA’s prohibition on off-label promotion, physicians are free to use their medical judgment to prescribe approved medications for off-label uses, however, drug manufacturers are prohibited from marketing their products for indications that have not been approved by FDA.
Although treatment in the “persistently high” population has not been approved by FDA, Amarin claims to have conducted studies showing favorable effects of Vascepa in patient populations with persistently high triglyceride levels. Despite these findings, FDA has never approved Vascepa for use in this population, and FDA advised Amarin that promoting this drug for use in patient populations that experience consistently high triglyceride levels constitutes “off-label promotion.” FDA prohibited the promotion of Vascepa for this off-label use, the violation of which could have cost Amarin millions of dollars in criminal and civil penalties.
This prohibition, Amarin claimed, is a violation of Amarin’s constitutional rights to truthful speech and Amarin sued for declaratory judgment to make certain truthful yet off-label statements about Vascepa. Amarin alleged that FDA’s threat of a misbranding action would be “chilling” Amarin from engaging in constitutionally-protected, truthful speech. Judge Paul Engelmayer agreed with Amarin, in view of a Second Circuit holding in United States v. Caronia, clarifying that Amarin is permitted to make specific, truthful statements about the off-label usages, including a caveat that the uses are backed by “supportive, but not conclusive research.” Amarin issued a press release declaring this decision a “victory aimed at improved patient care” and hopeful Amarin spokespersons stated that this decision “underscores the need for the FDA to rethink and make changes in how it regulates medical information.”
Despite this victory for Amarin, FDA’s jurisdiction over truthful, non-misleading off-label marketing still remains uncertain. The tension between FDA’s off-label promotion rules and the First Amendment’s protections for commercial speech have been highlighted in a handful of cases, with mixed results. See, for example, an article following Caronia. Here, Vascepa’s uniquely-favorable safety profile (comparable to fish-oil supplements) may have given it in an advantage. Judge Engelmayer concluded that there was no reason to fear that this particular off-label purpose would “endanger the public health,” contrary to FDA’s assertion that various proposed Amarin statements “would be potentially harmful to the public health, and [the] FDA would consider such conduct to be potentially misleading.” He added, “The Court’s approval today of these communications is based on the present record. Amarin bears the responsibility, going forward, of assuring that its communications to doctors regarding off-label use of Vascepa remain truthful and non-misleading.” Regarding truthful off-label promotion, FDA promised to issue new guidance in June of last year but has not issued new guidelines for industry yet. Drug manufacturers may need to tread carefully during this period of uncertainty regarding truthful, non-misleading off-label promotional practices but may now have some more options to consider.