The U.S. Food and Drug Administration (FDA) and Amarin Pharma, Inc. (Amarin) have released a stipulation and settlement order that would resolve all causes of action raised in Amarin’s successful lawsuit against the agency, with both parties waiving the right to appeal.

On August 7, 2015, the U.S. District Court for the Southern District of New York had granted Amarin a preliminary injunction declaring that the company may engage in truthful and non-misleading speech promoting an unapproved use of Vascepa® (icosapent ethyl).  Hogan Lovells previously covered the August 7, 2015 order here.  Importantly, the proposed settlement order leaves the court’s August 7, 2015 order intact and specifies that the settlement should be interpreted consistently with that order.

In addition the settlement emphasizes that FDA “agree[s] to be bound by the court’s conclusion that Amarin may engage in truthful and non-misleading speech promoting the off-label use of Vascepa,” and that “nothing in this [settlement] shall be construed to limit Amarin’s constitutional rights to free speech concerning Vascepa.”  Citing Caronia, the settlement agreement confirms that truthful and non-misleading speech about an unapproved use of Vascepa may not form the basis of a prosecution for misbranding.

A Novel Review Procedure

An interesting aspect of the settlement is that it establishes a novel procedure through which Amarin can seek feedback from FDA regarding proposed communications about Vascepa.  The settlement specifies that in addition to generally available procedures for submitting proposed communications to FDA for comment,  Amarin may submit up to two proposed communications per calendar year, and FDA agrees that it will respond with its specific concerns or objections within 60 calendar days (or longer if agreed by the parties).  Amarin will respond, in turn, within 45 days (or longer if agreed by the parties), and within 30 days of Amarin’s response FDA will notify Amarin of any remaining dispute.  At that point, either party may file a motion with the SDNY to resolve the dispute.  Notably, this review procedure is optional (i.e., Amarin is not required to use this mechanism to receive pre-clearance of its communications) and time limited, expiring on December 31, 2020—although this timeframe extends well beyond the anticipated completion of the REDUCE-IT outcomes trial in 2018.

The settlement also specifies a dispute resolution process if the parties cannot resolve any other “dispute on matters arising under this [settlement order].”  Under this process, an aggrieved party must provide written notice to the other party of a dispute, and the other party has 60 calendar days to cure or resolve the issue.  If the aggrieved party is not satisfied, it must provide notice and a specific response within 30 days.  If there is no resolution at the end of this procedure, either party may file a motion with the SDNY requesting judicial resolution.  Notwithstanding this process, the settlement permits FDA to communicate with doctors through “whatever channels FDA deems appropriate” regarding a dispute covered by this provision.  Thus, it appears that the settlement preserves FDA’s ability to act if, for example, it believes that a disputed issue presents a threat to the public health.  The settlement does not specify a sunset date for this dispute resolution process.

These unusual judicial resolution provisions suggest that the parties may anticipate the possibility of substantial disagreements in the future about what constitutes truthful and non-misleading speech; moreover, they could render the SDNY an active participant in defining the scope of permissible communications about Vascepa going forward..

Potential Implications

The proposed settlement forecloses FDA’s opportunity to appeal the August 7, 2015 order and reaffirms Amarin’s constitutional rights to certain truthful and non-misleading claims concerning Vascepa.  These developments may provide additional confidence to companies considering similar communications while we await FDA’s clarification of its policy regarding communications about unapproved uses.  At the same time, the settlement does not address important questions raised by the August 7, 2015 order, including a more generalizable articulation of the parameters of “truthful and non-misleading” speech that is protected by the First Amendment.

As a practical matter, it remains unclear how closely tied the settlement’s principle is to the specific facts of this case.  In issuing the August 7, 2015 order, the court acknowledged that it was able to evaluate whether the specific statements Amarin proposed to make about Vascepa were truthful and non-misleading because of the extensive administrative record available from FDA’s review of the ANCHOR study and Amarin’s supplemental new drug application.  For other drugs, the parameters of truthful and non-misleading speech about an unapproved use may be harder to define in the absence of such a record.  Although the results of adequate and well-controlled studies evaluating unapproved uses may be a sound basis for promotion with appropriate disclaimers, it is unclear whether promotion based on other types of studies or data would be regarded as either truthful or non-misleading by FDA or the courts.  Additional circumstances, such as a drug’s safety profile and the ability to draft appropriate disclaimers, may influence the ability to extrapolate the terms of the Amarin settlement to other drugs.  To the extent FDA and Amarin utilize judicial resolution, as provided under this settlement, we may gain further insights into the contours of truthful and non-misleading promotional speech about unapproved uses.

For companies considering Amarin-like communications, the settlement provides a reminder that they may submit proposed communications to FDA for comment under 21 CFR 202.1(j)(4).  Although the settlement’s novel feedback procedure, with specified timelines and an option for judicial resolution, is available to Amarin only, it is interesting to consider whether FDA may adopt this type of mechanism as a feature of its policy, moving forward, regarding promotional communications about unapproved uses of approved drugs or if it might consider other mechanisms floated by external groups recently, such as a third party expert panel to review and provide comments on such communications.

The settlement also reaffirms that Amarin and any other company that may choose to engage in Amarin-like communications bears the burden of assuring that its communications remain truthful and non-misleading over time.  As science evolves and more studies are published, what was once truthful and non-misleading could become misleading because of emerging context or data that is not sufficiently disclosed. This means that companies considering Amarin-like communications must monitor scientific developments closely and be nimble about revising claims and disclaimers accordingly and training their field representatives to do the same.  As a practical matter, it also emphasizes the need for rigorous training and monitoring to ensure that execution in the field is incontestable.