Pharmaceutical Manufacturer's Preemptive Suit Secures Preliminary First Amendment Protection For Script To Promote Off-Label Use

On August 7, 2015, the U.S. District Court for the Southern District of New York invoked the First Amendment, granting Amarin Pharma, Inc. (Amarin) preliminary protection against federal criminal prosecution for misbranding and allowing Amarin to promote its drug, Vascepa, for off-label use through certain truthful, non-misleading speech.1 In so ruling, Judge Engelmayer applied the Second Circuit's widely cited precedent in Caronia, which overturned a conviction under the same statutory provision.2 The extension of the much-scrutinized Caronia rule to a novel procedural posture raises important considerations for compliance officers and other staff in the pharmaceutical industry.

Factual Background

In 2012, Amarin obtained FDA approval for Vascepa to treat adults with “very high” triglycerides (defined as over 500 mg/dL of blood). Very high triglycerides are associated with increased risk of cardiovascular disease, so drugs that reduce triglycerides were expected to reduce the risk of cardiovascular events. Vascepa is a purified Omega-3 fatty acid product, derived from fish oil. Similar products are marketed directly to consumers by other companies under the FDA's less-stringent dietary supplement regulations.

Amarin sought approval for Vascepa to treat adults with lower but still-high triglyceride levels (200 to 499 mg/dL) who are already being treated with statins for cholesterol (“persistently high” triglycerides). Vascepa passed an additional clinical trial in 2013, but the FDA withheld approval because studies using other, unrelated triglyceride-reducing drugs found that reduced triglycerides did not reduce the risk of cardiovascular events. FDA delayed approval pending the outcome of yet another study in which Amarin was already participating, designed to test directly Vascepa's impact on risk of cardiovascular events. FDA warned Amarin not to promote Vascepa off-label, or risk prosecution.

Legal Background

The Food, Drug, and Cosmetic Act (FDCA) contains a criminal provision against selling (in interstate commerce) any drug that is “misbranded,”3 which the FDCA defines as lacking “adequate directions for use.”4 FDA regulation interprets as “adequate” directions that a layperson can use to take the drug safely “for the purposes for which it is intended.”5 The same regulations interpret “intended use” as the “objective intent” of the manufacturer, as demonstrated by oral and written statements and whether the drug is “offered and used for a purpose for which it is neither labeled nor advertised” with the manufacturer's knowledge.6 The FDA takes the position that off-label promotion alters the “intended use” of the drug, rendering a drug misbranded.

The FDA has further taken the position that the truthfulness of the off-label promotion is irrelevant, since the prosecution is for the misbranded sales, not the promotional speech. In U.S. v. Caronia, however, the Second Circuit overturned the misbranding conviction of Alfred Caronia, a pharmaceutical representative, on First Amendment grounds.7 After looking closely at the trial record, the Second Circuit determined that in effect, Caronia had been convicted solely on the basis of his speech. Applying the Central Hudson test8 for commercial free speech, the Second Circuit found that the misbranding offense would violate the First Amendment, because it fails to directly advance the...