Will FDA’s Settlement With Amarin Weaken Agency Oversight of Off-Label Promotion?

The US Food and Drug Administration and Amarin Pharmaceuticals have reached a settlement allowing the drug company to market their prescription-grade omega-3 fatty acid, known as Vascepa, for off-label use.

The settlement follows a favorable August 2015 decision from a federal district judge in Manhattan who ruled the FDA could not stop Amarin from talking to physicians about the off-label use of Vascepa, a purified ethyl ester of eicosapentaenoic acid (EPA) derived from omega-3 fatty acids, as long as the company provided “truthful and non-misleading” information to physicians.

Amarin made the case—and the federal court agreed—that such discussions are protected under their right to free speech.

The settlement itself still needs to be approved by the court, but the FDA issued a statement to TCTMD and other media outlets, saying that given the “unusual circumstances” of the case, and the scientific information presently known to the FDA, they do not anticipate the agreement will have substantial adverse impact on public health.

On Tuesday, Amarin issued their own press release, saying the “settlement serves the public interest by supporting informed medical decisions” for patients with elevated triglycerides. More importantly, the release reads, the “expanded promotion” of Vascepa, which the company initiated following the favorable ruling from the federal court, will continue as planned.

Despite Amarin’s rosy interpretation of the settlement, others were less charitable, worrying the decision will weaken the FDA’s ability to police the behavior of industry promoting off-label use.

“Personally, I think this ruling while ‘legally’ and ‘constitutionally’ correct could potentially end up opening up a Pandora’s box that will likely burden the already stretched FDA with additional workload and detract from its mission of promoting innovation without compromising public safety,” Sanjay Kaul, MD (Cedars-Sinai Medical Center, Los Angeles, CA), told TCTMD in an email.

James Stein, MD (University of Wisconsin, Madison), called the federal decision and subsequent settlement a “horrible precedent.”

“Drug companies have a horrible history of misleading advertising, misleading research, and stretching the legal limits of what they can market,” he stated in an email to TCTMD. “This ruling makes it easier for them to do so. They are stepping into the FDA’s job. And in the end, make no mistake about it, the public will pay for the profits the pharmaceutical companies accrue while waiting to show that their drugs actually improve real outcomes, rather than surrogates like triglycerides levels.”

Slippery Slope

With their drug currently approved for use in a small group of patients with extremely elevated triglyceride levels (> 500 mg/dL), the Dublin-based Amarin sued the FDA in 2015, arguing they had a constitutional right to promote Vascepa to a broader range of patients.

The company has thus far failed to convince the FDA to extend the label beyond those with severe hypertriglyceridemia. In 2013, Amarin submitted a supplemental new drug application (sNDA) to the FDA to extend the indication to adult patients with mixed dyslipidemia and triglyceride levels ranging from 200 to 499 mg/dL, but the FDA Endocrinologic and Metabolic Drugs advisory committee voted against approving the new indication. At the time, the agency advisors felt certain Vascepa lowered triglyceride levels, but said there was not enough evidence to show that lowering triglycerides lowered the risk of cardiovascular events.

To TCTMD, Kaul said that based on the 2013 sNDA, the population of eligible patients—those with triglycerides >200 mg/dL and existing cardiovascular disease or at high risk for cardiovascular disease—would have expanded to approximately 20% of the US population. “Even though the FDA denied the proposed new indication, the drug is available on the market and physicians are free to prescribe it off-label,” said Kaul. Now, with the settlement, the sponsors will be allowed to promote such this kind of use.

Just a few weeks ago, a federal jury acquitted Vascular Solutions and its CEO Howard Root of charges of off-label promotion of that company’s device for the treatment of varicose veins. These rulings, said Kaul, appear to “suggest that the federal government has abandoned the idea that truthful and non-misleading off-label promotion can be criminal.”

Kaul pointed out that the label clearly states that while there is evidence Vascepa lowers triglycerides in patients with levels > 200 mg/dL, the effect of Vascepa or triglyceride-lowering by any other drug on cardiovascular risk has not been determined. “If the company sticks to this promotion, I don’t have any problems with that,” he said.

The ongoing REDUCE-IT study is slated to tackle the clinical efficacy of Vascepa, with results from the 8,000-patient trial expected in late 2017 or early 2018. The primary endpoint is a composite of cardiovascular death, MI, stroke, coronary revascularization, and hospitalization for unstable angina. Another trial, known as STRENGTH, is also testing whether adding fish oil, in this case an omega-3 carboxylic acid (Epanova, AstraZeneca), to statin therapy reduces the risk of cardiovascular events compared with a statin alone in patients with elevated triglycerides (≥ 180-499 mg/dL). Results from that trial won’t be available until 2019.   

Source:        
Amarin Pharmaceuticals. Amarin's Right to Promote Vascepa Off-Label Affirmed Under First Amendment Litigation Settlement Terms. http://investor.amarincorp.com/releasedetail.cfm?ReleaseID=959511. Published on: March 8, 2016. Accessed on: March 9, 2016. 

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