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Regulatory Focus™ > News Articles > 2019 > 11 > FDA Advisory Committee Votes Unanimously in Favor of Expanding Amarin’s Vascepa Label

FDA Advisory Committee Votes Unanimously in Favor of Expanding Amarin’s Vascepa Label

Posted 14 November 2019 | By Zachary Brennan 

FDA Advisory Committee Votes Unanimously in Favor of Expanding Amarin’s Vascepa Label

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee on Thursday voted 16-0 to recommend that the agency expand the label of Amarin’s Vascepa (icosapent ethyl), a derivative of fish oil, to add an indication on reducing the risk of cardiovascular events.

The meeting was closely watched because the expanded label could push Vascepa, which six years ago received a negative opinion from this same committee on an expanded label, to blockbuster status. In 2018, Vascepa brought in about $229 million in net revenue.

This time, both FDA and Amarin highlighted how the primary and secondary endpoints were met in the REDUCE-IT trial on which the label expansion would be based, demonstrating statistically significant efficacy. New safety findings, including an increased risk of atrial fibrillation/atrial flutter and bleedings events from the trial, were also discussed by the panel.

Marvin Konstam, chief physician executive at the cardiovascular center at Tufts Medical Center, said he was not as concerned with the atrial fibrillation risks, but he was concerned about the bleeding, suggesting some sort of mitigation plan in the label. “The bleeding issue is real and it could be impacted by other antithrombotic agents,” he said. Others agreed that the specifics of the label should be left up to FDA.

Several panelists also said the trial evidence was not enough to support a claim for reducing cardiovascular deaths, while others questioned if Vascepa should be used for low-risk patients.

James de Lemos, distinguished chair in cardiology at UT Southwestern Medical Center, said he was unconvinced of Vascepa in primary prevention and that sponsor should not be rewarded for enrolling small subsets of primary prevention patients in a secondary prevention trial. “The drug should be approved for secondary prevention only,” he added, explaining how primary and secondary populations are different and not subgroups of one another.

John Sharretts, acting deputy director of FDA’s division of metabolism and endocrinology products, raised questions about the use of mineral oil placebo and how it may have exaggerated Vascepa’s benefits, although others indicated that the mineral oil placebo was unlikely to derail the study’s conclusion.

The questions on the use of such a placebo follow a perspective published recently on the REDUCE-IT trial that found an “ambiguous conclusion as to whether the benefit seen was because of the benefit of the drug or a harm from the specific control.”

In response to placebo questions, Amarin said at the meeting that it “could not definitively say that there was not a mineral oil effect, but we do not see any definitive evidence there was.”

Some of the panel members seemed to agree with FDA’s Sharretts on the lack of issue related to the mineral oil placebo, although one of the panelists noted it was a “nagging concern” and another one mentioned it as “the elephant in the room.”

Connie Newman, adjunct professor of medicine at New York University Langone School of Medicine, added that the amount of mineral oil people usually ingest is about 30 to 40 milligrams per day and the patients in the placebo arm of this trial ingested about 100 times that amount for five years. “It makes me question if this is more harmful than we’ve thought,” she said.

Ultimately, the panelists voted in favor of the label expansion, noting the sucess of the trial, although risk mitigation issues were discussed.

The advisory committee’s positive vote follows the recent publication of a survey in Circulation: Cardiovascular Quality and Outcomes that found doctors who received company information about the unapproved use of Vascepa were more likely to report prescribing it off-label. FDA and Amarin in 2016 settled a court case over the off-label promotion of Vascepa.

Co-author Aaron Kesselheim, professor of medicine at Harvard Medical School, told Focus: “I think one of the main findings of the study is that the marketing arrangement that the FDA and Amarin have been operating under until this point may not be having the intended effect in terms of how well it was putting prescribers on alert about what the evidence actually showed about the impact of Vascepa use.”

He also said he thinks that “simply using disclaimers as a way to insulate against the risks of off-label drug marketing is not sufficient – a broader evidence context would be more useful.”


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