Are Disclosures a Pathway to Off-Label Promotion?

I had the opportunity at FDLI’s Introduction to Drug Law and Regulation course to present on the implications of recent developments relating to off-label promotion — including the complaint filed in Amarin Pharma, Inc. v. FDA. Over the past several years, the Department of Justice and the Office of Inspector General (OIG) of the Department of Health and Human Services have teamed with the FDA to prosecute a number of high-profile off-label promotion enforcement actions.  These cases resulted in guilty pleas under the misbranding provision of the Food, Drug and Cosmetic Act (FDCA) and returned billions of dollars to government coffers under the False Claims Act (FCA).

First Amendment challenges to the FDA’s prohibition on off-label promotion by Amarin and a pharmaceutical sales representative in United States v. Caronia draw into question the future viability of such enforcement actions.  These challenges also may have the FDA considering additional pathways for off-label communication by pharmaceutical companies.  A key element of any such pathways may involve disclosures, offered up by both the Caronia court and the Amarin complaint as a more narrowly tailored means of limiting any harm that may result from off-label promotion.

The Amarin Complaint

In the Amarin complaint, the company alleges that the FDA’s interpretation of the misbranding provision of the FDCA unconstitutionally restricts its ability to promote truthful, non-misleading information about its product to physicians.  Section 352(n) of the FDCA states that a drug is misbranded unless its advertising includes a brief summary of the drug’s side effects, contraindications and effectiveness in a manner prescribed by FDA regulations.

FDA’s regulations prescribing the substance of an advertisement’s brief summary state that drug advertisements “shall not recommend or suggest any use that is not in the labeling accepted in such approved new-drug application or supplement” (21 CFR §202.1(e)(4)(i)(a)).  Amarin argues that this regulation impermissibly expands upon section 352(n) because it prohibits truthful and non-misleading speech about its products.

In particular, paragraph 199 of the Amarin complaint contends:

Under FDA’s application of [21 CFR §202.1(e)(4)(i)(a)], any direct-to-physician advertisement suggesting the off-label use of Vascepa®, regardless of the nature or quality of disclosures by Amarin to healthcare professionals, is per se unlawful.

In making this allegation, Amarin is clearly referencing the Second Circuit’s application of the Central Hudson test its Caronia opinion.

Caronia Alternative — Disclosures

In Caronia, the Second Circuit overturned the conviction of a pharmaceutical sales representative charged with violating the FDCA’s misbranding provision through the off-label promotion of his company’s drug.  The court concluded that the government prosecuted Caronia for his speech and ruled that the misbranding provision of the FDCA does not prohibit truthful off-label promotion of approved drugs.  Therefore, the court declared the government’s enforcement action against Caronia to be an unconstitutional restraint on the exercise of free speech.

In reaching its decision, the Second Circuit applied traditional First Amendment analysis to the enforcement action against Caronia, namely the Central Hudson test.

In particular, the Caronia court held that the restriction on off-label promotion was not narrowly drawn – the third prong of the Central Hudson test.  The court identified a number of possible alternatives short of restricting speech that the government could employ to achieve its objectives of ensuring drug safety and protecting the public health.  Among the alternatives mentioned by the court was the use of disclosures to qualify off-label promotion.

More Speech — Not Less

This brings us back to the Amarin complaint, which specifically sets out the types of disclosures that the company would make in promotional materials containing information about off-label uses for its product.  Amarin indicated it would disclose that its product was not FDA approved for the uses discussed in the information that it wished to disseminate, including information relating to a study demonstrating its efficacy for the off-label use.

Given the statement in the Caronia decision regarding disclosures as a more narrowly tailored alternative to the prohibition of truthful, non-misleading off-label promotion, the District Court for the Southern District of New York – which will consider the Amarin complaint and which lies in the Second Circuit – may be sympathetic to Amarin’s position.

The FDA recently announced that it will hold a public meeting to further consider its position on off-label promotion — the agency already granted two citizen petitions seeking clarity on its position.  The use of disclosures is likely to be a topic of discussion at the FDA public meeting.  Time will tell if the agency shows any willingness to create a pathway for truthful and non-misleading off-label promotion that incorporates the use of appropriate disclosures.