While the recent Second Circuit holding in US v. Caronia may be interpreted by some as a significant decision impacting off-label promotion of prescription drugs, it may well be premature for manufacturers to modify compliance policies prohibiting off-label promotion based solely on Caronia. The Caronia case was an appeal of a criminal prosecution of a drug sales representative who had been convicted of conspiring to introduce a “misbranded drug into interstate commerce.” The sales rep was promoting the drug Xyrem for unapproved indications (e.g. muscle disorders and chronic pain) and unapproved subpopulations (e.g. patients under age sixteen). The Court vacated the conviction on the theory that it was a supposed violation of the First Amendment.

The decision, in many respects, appears to create more questions about off-label marketing than it answers. The Second Circuit interprets the Federal Food Drug and Cosmetic Act (FDCA) to permit “truthful” off-label promotion of drugs and devices; however, this leads to the unanswered question: What is truthful off-label promotion?  And, is it possible to conduct “truthful” off-label promotion in the absence of adequate and well-controlled studies supporting such “truthful” promotion?  The Caronia ruling should be viewed narrowly because the very nature of the off-label promotion at issue was, in and of itself, what resulted in the violation.  The Second Circuit vacated the conviction effectively finding that the promotion could not be a proxy for off-label use or the specific intent to misbrand.

The Court leaves intact for another day the question of whether the underlying speech can be evidence that the company is engaging in off-label use or intent to misbrand (versus promotion), which may still be a violation. That is, the ruling says that promotion by speech may be protected, but does not actually decide if the speech is evidence of use. In addition to the possibility of judicial review, the Second Circuit holding calls into question the very foundations of our century-old system of drug regulation. The dissent takes a position that may be more tenable, and does not believe that the Supreme Court’s precedents, relied on in the majority opinion compel a result that has the First Amendment trumping laws against off-label promotion. The significance of this case suggests that there may be at least an en banc review of the majority holding.  If the decision stands, the FDA and government enforcement agencies may well produce guidance that narrowly defines the bounds of truthful speech by sales representatives. In the final analysis, companies would be prudent to promote only those therapeutic uses that are supported by adequate and well controlled studies.