Court Rules That Amarin’s Proposed Promotion of an Unapproved Use For Vascepa is Protected by the First Amendment
On August 7, 2015, the U.S. District Court for the Southern District of New York ruled in favor of Amarin Pharma, Inc. (Amarin) in its suit against the U.S. Food and Drug Administration (FDA).1 The court granted Amarin’s motion for preliminary relief, declaring that Amarin may engage in truthful and non-misleading speech promoting an unapproved indication of Vascepa (icosapent ethyl), and that such speech may not form the basis of a prosecution for misbranding because it is protected commercial speech under the First Amendment.
This opinion is the latest in a series of First Amendment setbacks to FDA’s application of the prohibition on misbranding in the Federal Food, Drug, and Cosmetic Act (FDCA). Applying the commercial speech doctrine, the District Court rejected FDA’s assertion that the FDCA allowed a categorical ban on promotional statements regarding data and information about an unapproved use of Vascepa. The Court also expressly ruled that several proposed statements about that use were truthful and non-misleading.
While this decision is significant, several factors caution against near-term or wholesale changes to companies’ promotional policies and practices. First, the order awards preliminary relief to Amarin pending the court’s final determination of the case on its merits. The outcome may change after additional discovery and litigation.2 Second, this case addresses a very specific set of facts that may influence the potential implications of this ruling (e.g., the product is a fish oil derivative that poses few risks to patients, and the unapproved use at issue was studied under an adequate and well-controlled design vetted by FDA). Third, Amarin’s proposed promotional statements are narrowly focused on the study results and accompanied by several disclaimers. And, finally, although the court takes issue with FDA’s narrow reading of Caronia (as discussed below), it makes clear that its holding only covers situations where truthful and non-misleading speech is the sole basis for prosecution.
FDA approved Vascepa in 2012 “as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.”3 Subsequently, Amarin submitted a supplemental new drug application (sNDA) for a second indication: treatment of patients with persistently high triglyceride levels from 200 to 499 mg/dL who are already on statin therapy. The sNDA relied on a trial that successfully demonstrated that Vascepa reduced triglyceride levels in patients with persistently high triglycerides.
Nonetheless, the agency refused to approve the sNDA, issuing a Complete Response Letter (CRL) in April of this year.4 In the CRL, the agency stated it could not approve the sNDA in light of recent clinical trial data suggesting that a reduction in triglyceride levels may not serve as an adequate surrogate for a reduction in cardiovascular risk.5 Most importantly, the CRL warned Amarin that Vascepa “may be considered to be misbranded under the [FDCA] if it is marketed with this change before approval of this supplemental application.”6 In response, in May of this year, Amarin and four New York-based physicians sued FDA seeking, among other things, a declaratory judgment that Amarin has a First Amendment right to engage in truthful and non-misleading speech about the use of Vascepa in patients with triglycerides between 200 and 499 mg/dL without fear of criminal prosecution or civil liability.7
Agreeing with Amarin, the court’s opinion was based largely on the United States Court of Appeals for the Second Circuit’s 2012 ruling in United States v. Caronia, which addressed the relationship between the First Amendment and the FDCA’s misbranding provisions.8 In Caronia, the court overturned the conviction of a sales representative for conspiracy to introduce a misbranded drug into interstate commerce.9Vacating the conviction, the Second Circuit held that the representative’s truthful and non-misleading speech was constitutionally protected, and that the FDCA’s misbranding provisions do not criminalize the promotion of a drug for off-label use based on speech alone because such a construction would run afoul of the First Amendment. The Circuit explained that “[t]he government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug.”10 For more information on Caronia, see our previous Hogan Lovells Client Alerthere.
The Amarin Opinion
During the Amarin proceedings, FDA argued that Caronia should be interpreted narrowly, such that the agency still had the power to bring a misbranding charge against a manufacturer and its representatives for promoting an unapproved use of a drug. FDA asserted that Amarin’s proposed use of certain peer-reviewed literature regarding adequate and well-controlled clinical trials was permissible under its Good Reprints Practices Guidance. But FDA stopped short of allowing all of the claims Amarin proposed. In particular, FDA asserted that a proposed statement regarding the clinical outcomes that might result from triglyceride lowering would be considered potentially misleading and potential evidence of intended use.11
The Amarin court disagreed that the ruling in Caronia was a narrow one. Rather, the Amarin court appliedCaronia broadly, stating emphatically that “FDA may not bring [a misbranding] action based on truthful promotional speech alone, consistent with the First Amendment.”12 The Amarin court observed thatCaronia had undertaken a thorough First Amendment analysis of the statutory misbranding provisions and concluded that they did not apply to promotion of an unapproved use, when the promotion consists of only truthful, non-misleading speech. The holding in Caronia was therefore "a definitive one of statutory construction," as opposed to being limited and fact-specific.13
In addition, the Amarin court rejected FDA's contention that under Caronia only certain types of truthful speech were protected under the First Amendment from charges of misbranding. Specifically, FDA claimed that truthful statements about unapproved uses made proactively by sales and marketing employees were not protected under the First Amendment.14 The Amarin court disagreed that such restrictions are defensible under the First Amendment, noting that “the reasons the Circuit gave in Caronia for that holding apply across the board to all truthful and non-misleading promotional speech.”15 At the same time, the court underscored that Caronia does not foreclose misbranding prosecutions under certain circumstances, including where communication about an unapproved use is false or misleading: “Caronia holds protected, and outside the reach of the FDCA’s misbranding provisions, off-label promotion only where it wholly consists of truthful and non-misleading speech.”16
After determining that the First Amendment protects Amarin’s proposed discussion of the use of Vascepa in patients with persistently high triglycerides, the court proceeded to assess Amarin’s proposed claims and disclaimers. This analysis is perhaps the most informative in assessing the implications of the decision. The court spent approximately 13 pages examining the parties’ proposed language, making the point quite clearly that the devil is in the details when it comes to determining which scientific points are both truthful and non-misleading.17 The court rejected many of both parties’ assertions regarding the conclusions of the scientific inquiry into triglyceride lowering to date.18
And the court explicitly limited its holding in at least two ways. First, the court noted that the First Amendment covers expressions and not conduct. In other words, a company that “engages in non-communicative activities to promote off-label use cannot use the First Amendment as a shield.”19 The court’s opinion refers to a hypothetical that was discussed at oral argument in which a company pays doctors or buys doctors resort vacations as purported rewards for prescribing a drug for an unapproved use. In such a context, the court notes that promotional statements regarding an unapproved use could be admissible as evidence of intent to misbrand a drug to the extent such statements “shed light on the intent behind these actions or to present the scheme in context.”20 Second, as discussed above, speech that is false or misleading is not protected.21 Although the court ultimately determined that Amarin’s proposed statements, as modified, were truthful and not misleading, the court did not offer more general views about what factors could influence whether speech about an unapproved use is misleading or non-misleading. Whether speech is “false or misleading” may be difficult to discern, leaving FDA an opportunity to assert its judgment.
As the litigation continues, further developments in the Amarin case—and potential developments elsewhere—will be important to watch. For example, while this decision may open the door for companies to communicate truthful and non-misleading information about unapproved uses beyond FDA’s existing reprints guidance, the parameters of “truthful and non-misleading information” remain ill-defined. The facts in this particular case suggest that information about the results of adequate and well-controlled studies that evaluate unapproved uses of approved products (even where the studies are not sufficient for approval) can fall within this category. However, the court’s decision does not address a number of related questions, such as whether information about studies other than adequate and well-controlled studies could fall within the category of truthful and non-misleading information.
In any event, any statements about an unapproved use undoubtedly will be subject to a high level of scrutiny. Thus, it may be prudent to convey objective statements of study results rather than characterizations of or elaboration about those results, which may be subjective and more prone to interpretation as misleading.
Also, the court made the point that companies will be responsible for ensuring that promotional statements remain truthful and non-misleading, particularly in the face of evolving science.22 Companies will need to monitor new developments closely and revise their claims accordingly. Adopting the Amarin holding may pose higher risk for products with significant safety issues and in cases where FDA has not examined the studies at issue. Especially in these situations, companies may want to consider seeking advance guidance from FDA, as the court suggested.23 We also recommend involving product liability counsel in discussions about the nature of these communications, given that FDA review and approval of drug labeling provides a substantial shield to plaintiffs’ failure to warn claims.
Finally, going forward, the ruling may cause FDA and DOJ to focus even more heavily on non-speech activities, such as financial arrangements with healthcare professionals and sales representative compensation. As described above, the Amarin court noted that sales representative speech about unapproved uses of a product, while not itself subject to restraint, can be admissible to demonstrate that payments to healthcare professionals are intended to reward off-label uses of a product.24
For more information about the Amarin holding or drug promotion enforcement more generally, please contact the authors or the Hogan Lovells lawyer with whom you work.
The opinion is available here.