Introduction

On August 7 2015, in a widely anticipated ruling in the ongoing Amarin litigation against the US Food and Drug Administration (FDA),(1) Judge Engelmayer granted Amarin's general and specific requests for relief. This ruling forcefully rejected the government's assertion that the Second Circuit's decision in United States v Caronia(2) does not preclude a misbranding action "where the acts to promote off-label use consist solely of truthful and non-misleading speech". "The Court's considered and firm view," it held, "is that, under Caronia, the FDA may not bring such an action based on truthful promotional speech alone, consistent with the First Amendment." Amarin thus rejects the limited interpretation of Caronia that the government has been advancing for nearly three years – but the decision is more than just the 'son of Caronia'.

Court rejects FDA's argument

Of major significance for FDA-regulated manufacturers, to an even greater extent than the Caronia decision itself, Amarin addresses – and rejects – the FDA's frequently articulated rationale that it must be allowed to regulate truthful, non-misleading off-label speech about drugs in order to protect the integrity of the drug approval process and thereby safeguard public health. The court acknowledged the FDA's contention that permitting truthful off-label speech constitutes a "frontal assault... on the framework for new drug approval that Congress created in 1962", but explained that the 1962 legislation creating the existing drug-approval scheme simply "predates modern First Amendment law respecting commercial speech". The court emphasised that the Federal Food, Drug and Cosmetic Act's misbranding provisions "must be considered, and to the extent ambiguous construed, in light of contemporary First Amendment law, under which truthful and non-misleading commercial speech is constitutionally protected". Moreover, the court twice pointed to the government's own failure to seek further review of the Caronia holding, through rehearing or certiorari, as evidence that the government's rhetoric about the impact of that decision was overblown.

More specifically, while accepting the FDA's position on the need for the 1962 drug amendments to stem the tide of false and misleading drug promotion – even citing Congressman Waxman's later published version of the legislative history – the court nevertheless categorically rejected the FDA's assertion that adopting Amarin's First Amendment position would eviscerate the new-drug approval process, with consequences for public health. Indeed, in weighing the familiar factors bearing on eligibility for preliminary relief, the court found that taking Amarin's side on the First Amendment point advanced the public interest, observing that "securing First Amendment rights is in the public interest". Moreover, the court took pains to describe the FDA's lack of authority to regulate physician prescribing practices and the widespread nature and public health value of off-label use of prescription drugs in a variety of settings, including oncology and paediatrics.

Court adopts disclaimer approach

Both thematically and in effect, the court's decision makes clear that the Federal Food, Drug and Cosmetic Act's new-drug approval requirements and the First Amendment can be reconciled under a disclaimer-based regime that reflects the notion that patient care is advanced, rather than undermined, by accurate off-label information. In granting Amarin's motion, the court declared that:

  • Amarin could promote its drug Vascepa (icosapent ethyl) for the off-label indication of treating patients with persistently high triglycerides, without that speech forming the basis of a misbranding prosecution; and
  • Amarin's specific proposed statements (with accompanying contextual information as modified by the court) were truthful and non-misleading.

Notably, the court authorised Amarin's proposed use of a qualified coronary heart disease risk-reduction statement, which the FDA had concluded that Amarin could not make for Vascepa based on the FDA's conclusion that such a statement would be potentially misleading. The court rejected the FDA's position and rationale, concluding instead that the statement (accompanied with a disclaimer) is "undisputedly an accurate account of the current state of scientific research". The court also permitted Amarin's proposed summary of a clinical trial designed to test the effectiveness of Vascepa in treating persistently high triglyceride levels, describing Amarin's dissemination of the study and its results "as neither false nor misleading".

Both the FDA's highly unfavourable win-loss record in First Amendment cases and the facts of the Amarin case made the FDA's defeat at the district court level inevitable. The opinion notes numerous aspects of the company's engagement with the FDA that highlight the constitutional infirmities in the FDA's administration of its regulatory scheme with respect to Vascepa. In particular, the court noted the FDA's decision to make approval of the supplemental indication contingent on a further clinical trial designed to generate data on a related endpoint – a point of interest to the FDA but not necessary to vindicate:

  • the accuracy of the speech;
  • the entitlement of dietary supplement manufacturers to make the same claim about cardiovascular risk reduction that the FDA had concluded Amarin could not make for its drug version of a closely related fish oil-derived ingredient; and
  • the FDA's rejection of the coronary heart disease risk-reduction hypothesis for Vascepa based on data from outcome studies of other, unrelated lipid-lowering products.

The court also pointed to the FDA's failure to provide timely guidance on manufacturer communications about regulated products. This was despite its promise to do so within a year of its June 2014 response to the Medical Information Working Group's 2011 and 2013 citizen petitions that requested action on off-label promotion-related issues. Moreover, the court accepted the FDA's assertion that off-label use can sometimes cause harm, but emphasised the baselessness of any fear that encouraging the use of Vascepa in treating patients with persistently high (but not severely high) triglyceride levels "would endanger the public health".

The decision does not answer all of the open questions about communication of off-label information. It does not address:

  • the proper interpretation of the FDA's regulations interpreting 'intended use';
  • the scope of the FDA's authority over labelling; and
  • the proper level of scrutiny Central Hudson's intermediate level of heightened scrutiny under Sorrell afforded government restrictions on accurate speech concerning lawful activities.

Nor does the opinion fully explicate the complex regulatory scheme that the FDA has developed to provide manufacturers with limited, carefully controlled outlets for off-label speech (eg, scientific exchange), or address the important due process deficiencies created by the ambiguity in the FDA's administration of the Federal Food, Drug and Cosmetic Act and its own implementing regulations.

Further implications for manufacturers

As a starting point, it is hard to see the government letting the decision stand if it remains committed to maintaining the current speech-restrictive regulatory scheme, and the district court's opinion evinces a care and thoroughness that clearly assumes that the matter will be taken up on appeal. Even while the litigation continues, however, manufacturers could (cautiously) evaluate their existing policies and procedures in view of the court's analysis. The court not only recognised manufacturers' entitlement to promote off-label using truthful, non-misleading statements and materials, but also rejected the FDA's request to permit only company scientists' responses to requests for off-label information, on the basis that proactive, promotional statements are "more likely to reflect a manufacturer's intent to promote off-label". Indeed, in rejecting the FDA's request, the court pointed out that the "the speech on which the Caronia prosecution itself was based involved the very types of statements promoting off-label use that the FDA most disfavors: proactive oral statements to a doctor by a manufacturer's sales representative".

As a result, there is a sound rationale not only in the underlying First Amendment decisional law, but also in the Amarin decision itself to conclude that sales representatives may lawfully engage in truthful, non-misleading promotion of an off-label use of an approved product. Although the Amarin decision itself is but a single district court decision in one judicial circuit, it reflects a compelling application of the principles explicated in Caronia. Further, both decisions are fully consistent with decades of case law repeatedly excoriating the FDA for overstepping constitutional limitations in regulating manufacturer speech and emphasising the First Amendment rule that the government is prohibited, as an absolute matter, from restricting truthful, non-misleading speech concerning lawful activities.

The decision has significant potential implications for ongoing regulatory proceedings. Despite a string of losses in First Amendment cases over the past three decades in multiple programme areas, the FDA's day-to-day actions and communications with regulated entities have consistently reflected hostility to speech rights. For manufacturers that are willing to bring proposed promotional materials to the FDA for prior comment, or that are otherwise engaged in correspondence with the FDA over the permissibility of their speech (eg, in response to enforcement correspondence), the decision in Amarin further buttresses arguments supporting a freer promotion using unlabelled clinical data. It will likely be necessary to advance the First Amendment point in the context of supervisory review, however, because of continued resistance to the notion of constitutional limitations on the FDA's authority over manufacturer speech at the programme level.

The decision also strengthens the hands of those manufacturers that are willing to bring their own First Amendment challenges. In rejecting the FDA's attempt to moot the dispute, the court pointed to boilerplate language from a complete response letter stating that Vascepa "may be considered to be misbranded under the [Federal Food, Drug and Cosmetic Act] if it is marketed with this change before approval of this supplemental application". The court indicated that "the FDA had expressly threatened...to bring a misbranding action against it [Amarin] for promoting Vascepa off-label, i.e., if Amarin marketed Vascepa for persons with persistently high triglycerides without approval of that use". Vague references to the possibility of misbranding liability are common in FDA correspondence and the court's emphasis on such language in finding a justiciable controversy should, in appropriate cases, alleviate manufacturer concerns about lack of standing or the failure of a complaint to present a ripe controversy.

Implications for FDA

The FDA must decide whether to continue to defend the constitutionality of the current regulatory regime or adapt its regulatory scheme to constitutional norms. In rethinking its public health role in view of evolving societal expectations and firmly established First Amendment limitations, the FDA will have to consider whether – contrary to many of its assumptions over the years – patient care can be enhanced by less regulation of manufacturer communications to physicians, payers and even patients. The FDA has a continued opportunity to clarify its regulatory scheme while also better aligning its rules with constitutional limitations by responding more fully to the two citizen petitions that the FDA granted last year.(3)

The FDA's task will not be easy, but it is essential. Senior officials within the FDA have doubtless been following developments in the First Amendment case law carefully, but lack of consensus among career personnel and the Department of Health and Human Services has precluded the FDA from taking firm steps to respond to industry requests for clarity and reform. The Amarin decision should encourage the development of that consensus. The FDA's history of extricating itself from First Amendment disputes without major programme modifications may embolden those inside and outside the FDA who are resistant to change – and the Amarin litigation has not yet concluded – but the decisions in both Caronia and Amarin point to the importance of immediate change. If the FDA cannot implement commonsense regulatory reform in response to the courts' continued application of well-established First Amendment principles to manufacturer speech about off-label uses, then Congress may have no choice but to modify the FDA's statutory authority. The alternative is continued judicial involvement in the review of proposed manufacturer promotional claims and the possible erosion of the FDA's role as the world's premier regulator of medical products.(4)

For further information on this topic please contact Coleen Klasmeier or Paul E Kalb at Sidley Austin LLP by telephone (+1 202 736 8600) or email (cklasmeier@sidley.com or pkalb@sidley.com). The Sidley Austin website can be accessed at www.sidley.com.

Endnotes

(1) 15 CIV 3588 PAE (USDC SDNY August 7 2015). For the full opinion please see http://www.sidley.com/~/media/uploads/AmarinOpinion.pdf.

(2) 703 F3d 149 (2d Cir 2012).

(3) For more information please see "Citizen Petition Grant".

(4) For more information please see "District Court Holds that First Amendment Bars Prosecution for Misbranding Where Conduct is Truthful, Non-Misleading Speech about Off-Label Uses, Declines to Rule on Potential FCA Liability".

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