Last month, I blogged on Amarin Pharma, Inc.’s complaint against the FDA challenging the agency’s regulations that prohibit the company from disseminating information about a drug’s “off-label” use.  See May Blog.  Since then, the FDA sent Amarin a response letter, which the agency argues greatly narrows the issues before the Court.  In addition, just last week, the FDA filed its opposition, going so far as to state that Plaintiffs’ sought relief “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[.]”

Although my prior blog post sets forth the facts at issue, the background on the suit is as follows (although this time, from the FDA’s perspective): The FDA approved Vascepa in 2012 for use relating to reducing the risk of pancreatitis from high triglycerides.  Since then, the FDA claims that Amarin has been attempting to obtain approval for a second use that relates to the reduction of the risk of cardiovascular events.  The FDA explains that Amarin conducted the ANCHOR trial, which was accepted by the FDA, despite the fact that the trial measured triglyceride levels and was not designed to directly measure cardiovascular outcomes.  New scientific data became available, however, which directly measured the effect on cardiovascular outcomes and revealed that the drug did not provide any additional benefits.  Consequently, the FDA concluded that there was insufficient scientific evidence that measuring triglyceride levels is an appropriate substitute for measuring cardiovascular outcomes in patients with high triglyceride levels who are already being treated with a statin.  As a result, the FDA rescinded its agreement regarding the ANCHOR trial.  Amarin is now conducting a second trial and expects results in 2018.

After failing to obtain FDA approval based on the ANCHOR trial, however, Amarin filed suit seeking an order to market the drug by disseminating summaries of the ANCHOR trial, journal articles, and a qualified health claim stating that supportive but not conclusive research shows that Vascepa may reduce cardiovascular disease.  In response, on June 5th, the FDA sent a letter to Amarin.  The letter explained that the agency “would not consider the dissemination of most of that information to be false or misleading” and that they “do not intend to rely on it as evidence that Vascepa is intended for a use that would render Vascepa an unapproved new drug or misbranded.”  The letter stated that the FDA would not object to the distribution of summaries of the ANCHOR trial and reprints of articles, so long as the company takes certain steps designed to prevent the communication from becoming misleading.  The FDA explained that to the extent Amarin chose to distribute reprints and summaries about unapproved uses in a manner not described in the letter, then the FDA may consider that as evidence of intended use that would render the drug misbranded.  Furthermore, the FDA expressed concerns about Amarin’s use of the proposed heart disease claim, which it found misleading and potential evidence that the company intends for the drug to be used to reduce the risk of heart disease – a use not approved by the FDA.

As a result of this letter, the FDA claims that the issues remaining in dispute are limited to Amarin’s proposed heart disease claim, and journal reprints and summaries of the ANCHOR trial results (only if disseminated in a manner that exceeds the scope outlined in their letter).  Thus, the FDA first argues that most of Amarin’s challenges fail to present an Article III case or controversy in light of the letter, which shows that with the exception of one communication at issue, the FDA would not rely on the communications in the complaint in an enforcement action.  The FDA asserts that Amarin therefore cannot show a credible threat of prosecution for the dissemination of information.

The FDA further argues that Plaintiffs are not entitled to a preliminary injunction because they are not likely to succeed on the merits because Amarin’s speech is not being unconstitutionally infringed.  The FDA explains that the issue is not whether it would be constitutional for the Federal Food, Drug, and Cosmetic Act (FDCA) to make truthful speech regarding unapproved uses a crime – because the FDCA does not do that.  Instead, the only issue is whether the First Amendment permits the Government to rely on Amarin’s dissemination of its proposed heart disease claim – in conjunction with its distribution of Vascepa – as evidence that it intends a new, unapproved use for the drug.  The FDA argues that the use of a company’s speech as a basis for inferring intent under the FDCA – which, the FDA claims is all that it has reserved the right to do in its June 5th letter – has been approved by courts on numerous occasions, and there is simply “no room for Amarin to argue that this evidentiary use of a manufacturer speech offends the First Amendment.”

Furthermore, the FDA argues that because courts do not consider the evidentiary use of speech to show intent to be a regulation of that speech, the Court need not consider if the FDA’s regulations pass constitutional muster.  But, the FDA argues that even if analyzed as commercial speech restrictions, the regulations nevertheless meet the test set forth by the Supreme Court in Central Hudson.  Under Supreme Court precedent, governmental restrictions are permitted if they advance a “substantial” government interest and are no “more extensive than is necessary to serve that interest.”  Central Hudson Gas & Electric Corp. v. Public Service Commission, 447 U.S. 557 (1980).  The FDA argues that applying the FDCA to the communications at issue would further important public health interests including for example, the Government’s interest in motivating robust scientific research, in ensuring that drugs bear labeling that is accurate and adequate, and in confirming that physicians have access to reliable information about the safety and efficacy of drugs.  Furthermore, the FDA argues that the FDCA as applied is narrowly drawn and fully consistent with the First Amendment since the June 5th letter makes clear that Amarin has numerous avenues to distribute truthful and non-misleading information relating to unapproved uses of Vascepa.

Lastly, the FDA argues that applying the FDCA to Amarin’s proposed communications does not violate their Fifth Amendment rights.  Specifically, the FDA argues that in light of its June 5th letter, Amarin cannot now hold the position that it has no notice of the conduct which could expose it to possible enforcement action.  FDA claims that given the letter, Plaintiffs “have more than sufficient notice as to what is permitted and what is not.”  Finally, the FDA argues that Amarin’s request that the Government be enjoined from enforcing the False Claims Act (FCA) against it is unnecessary and unwarranted.  Amarin explains that a false claim would not arise where the indication is actually supported by medical evidence and there is no other contention of falsity (which is what Plaintiffs allege).  Furthermore, the FDA explains that any FCA enforcement action would not implicate the First Amendment since the Act “does not prohibit speech; rather, it is a remedy for conduct that knowingly causes the submission of a false claim for payment to the government.”  Thus, the FDA asserts that Amarin is “simply wrong” in their contention that the company is at risk because its speech alone creates liability under the FCA.

Notably, Pharmaceutical Research and Manufacturers of America (PhRMA) and Medical Information Working Group filed amicus briefs in support of Plaintiffs’ request for an injunction, criticizing the FDA’s response and emphasizing that review is necessary.  For instance, PhMRA stressed in its brief: “Rather than solve the problem…the [FDA’s] letter only highlights the burden that FDA’s regulations regularly impose on manufacturers and the Agency’s invocation of its own vague and malleable discretion rather than publication of clear, binding guidance that comports with constitutional requirements.”  The brief blasts the FDA’s “recent made-for-litigation ‘regulatory letter’” claiming that it does not “cure constitutional defects” and merely reiterates “the Agency’s longstanding position that the FDCA and FDA’s implementing regulations prohibit manufacturers from speaking to healthcare professionals about unapproved uses.”