First Amendment Suit: FDA Draws The Line At Amarin's Heart Disease Claim

Trying to forestall preliminary injunction, FDA's Woodcock doesn't object to Amarin's reprint distribution, but says firm needs strong incentive to complete its cardiovascular outcomes study.

Amarin Pharmaceuticals Inc.’s suit seeking a court order to allow it to tell doctors about the unapproved use of its fish oil pill Vascepa (icosapent) “is a frontal assault” on the framework for new drug approval, FDA contends.

In a June 23 court filing opposing Amarin’s motion for a preliminary injunction, FDA says a decision in Amarin’s favor “has the potential to establish precedent that would return the country to the pre-1962 era when companies were not required to prove that their drugs were safe and effective for each of their intended uses.”

Amarin filed suit against FDA in May seeking a declaration that the agency’s regulations on off-label promotion are unconstitutional and that it has a right to distribute truthful and non-misleading speech about Vascepa “even if that speech is off-label promotion” (Also see "Off-Label Litigation: Amarin Sues FDA In Bid To Promote Vascepa Fish Oil" - Pink Sheet, 7 May, 2015.).

FDA disagrees with Amarin’s argument that regulation of its communications violates its First Amendment right to free speech.

The only issue before the court is whether the First Amendment permits the government to look at Amarin’s dissemination of information about unapproved uses “as evidence that Amarin intends a new use for Vascepa,” the agency states. “It unquestionably does: the evidentiary use of speech to prove intent is constitutional under the First Amendment.”

FDA sent Amarin a June 5 letter saying it would allow the company to distribute reprints of journal articles describing the results of the ANCHOR trial with appropriate disclosures (Also see "FDA “Approves” Amarin Vascepa Off-Label Campaign; Industry Groups Urge Court Not To Take The Bait" - Pink Sheet, 16 Jun, 2015.).

The agency says in its court filing that it does not object to most of Amarin’s proposed communications and that the only communications that remain in dispute are the claim about reduced risk of heart disease and journal reprints and summaries of the ANCHOR trials results that are not disseminated as FDA described in its letter.

REDUCE-IT Trial Could Be Derailed

FDA approved Vascepa, which consists of the omega-3 fatty acid eicosapentaenoic acid (EPA), in 2012 for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia. In April, FDA issued a “complete response” letter declining to approve the drug for use by adult patients on statin therapy with very high triglyceride levels based on the results of Amarin’s ANCHOR trial.

FDA said the company had not provided evidence of a reduction in cardiovascular risk. The company is conducting a cardiovascular outcomes trial in patients with high triglyceride levels, REDUCE-IT, the results of which are expected in 2018.

Amarin said it wants to be able to tell physicians about the results of the ANCHOR study right now and to provide peer-reviewed scientific publications “relevant to the potential effect of EPA on the reduction of the risk of coronary heart disease.”

FDA said dissemination of the heart disease claim in conjunction with the ANCHOR trial results would “perpetuate the unsubstantiated claim that Vascepa confers a clinical benefit by lowering triglyceride levels in patients with cardiovascular disease or risk.”

The agency is represented in the litigation by U.S. Attorney for the Southern District of New York Preet Bharara. Accompanying his 51-page memorandum is a 32-page declaration from Center for Drug Evaluation and Research Director Janet Woodcock describing the agency’s new drug approval requirements and the application of its policies on communication of unapproved uses to Amarin.

Curtis Rosebraugh, director of the Office of Drug Evaluation II, also submitted a declaration describing the agency’s approval of Vascepa, Abbott Laboratories Inc.’s Trilipix (fenofibric acid), AbbVie Inc.’s Niaspan (niacin extended-release) and GlaxoSmithKline PLC’s Lovaza (omega-3-acid ethyl esters) and the cardiovascular outcomes trials relevant to their labeling and approval.

Woodcock said that if the court were to authorize Amarin to make this claim the company would have much less of an incentive to conduct the REDUCE-IT trial.

“Although I understand that Amarin has stated that it intends to complete the REDUCE-IT trial, it is conceivable that Amarin might choose to forego the trial should it prevail in this lawsuit,” Woodcock said. “Were that to happen, the medical and scientific community would be deprived of the robust scientific data promised by the REDUCE-IT trial regarding the safety and efficacy of Vascepa for the use related to cardiovascular disease.”

Caronia Ruling Does Not Apply To Amarin, FDA Says

Amarin had pointed to the U.S. Court of Appeals for the Second Circuit’s 2012 ruling in United States v. Caronia in arguing its likelihood of success in the litigation. In that case the court held that the government cannot prosecute pharmaceutical manufacturers or their representatives for speech promoting the lawful, off-label use of an approved drug.

“Caronia, however, did not decide whether it would be constitutionally permissible for the government to consider speech to be evidence of intended use,” FDA states. “Instead, it involved the constitutionality of a ‘complete and criminal ban on off-label promotion.’”

“Moreover, unlike here, the Caronia court did not have the benefit of a government declaration demonstrating that the communications at issue might be misleading,” the agency stated. “And – also unlike here – the Caronia court was not presented with any declarations explaining how the communications at issue would undermine the premarket approval regime and attendant public interest it furthers, and why various potential alternatives would fail to protect those interests.”

Woodcock said FDA examined alternative approaches, including those identified by the Second Circuit in Caronia, and found that they were “impractical, ineffective, unrealistic, or based on inaccurate assumptions.”

These alternatives include an outright prohibition on the use of approved products for unapproved uses; creating ceilings or caps on the number of prescriptions for an unapproved use; limiting Medicare and Medicaid reimbursement to approved uses; prohibiting specific unapproved uses that are exceptionally concerning or developing tiers based on level of safety concerns; and allowing firms to promote an unapproved use as long as they disclose it is unapproved and include other warnings (Also see "FDA Reassessing Off-Label Policies To Address First Amendment Concerns" - Pink Sheet, 23 Apr, 2014.).

Amarin also asked the court to enjoin FDA from enforcing the False Claims Act against it for its proposed communications. FDA said that it is difficult to see how a false claim would arise if the indication cited is supported by a medical compendium and there is no other contention of falsity.

Besides, FDA said that to bring an FCA action, the government must prove that Amarin caused doctors to submit materially false claims to the government for payment of non-covered uses that were ineligible for payment and did so with knowledge of wrongdoing.