FDA Plans AdCom Meeting on Vascepa, Pushing CVD Approval

Megan Brooks

August 14, 2019

The US Food and Drug Administration (FDA) plans to hold an advisory committee meeting in mid-November in connection with its review of the hotly anticipated eicosapentaenoic acid (EPA) product, icosapent ethyl (Vascepa, Amarin), for cardiovascular (CV) protection, the manufacturer has announced.

It's expected that the planned November 14 advisory committee meeting will extend the original Prescription Drug User Fee Act (PDUFA) date by about 3 months, from September 28 to late December, Amarin said.

Vascepa is currently indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. Amarin's supplemental New Drug Application (sNDA) seeks to expand the label based on the REDUCE-IT CV outcomes study.

"At this time, Amarin expects topics to be reviewed at an AdCom meeting for the sNDA regarding Vascepa to be consistent with those discussed at similar meetings held by the FDA such as, but not limited to, topics covered as part of the publication of REDUCE-IT primary results in the New England Journal of Medicine and additional results published in the Journal of [the] American College of Cardiology, including review of the study conduct, populations studied, efficacy and safety," the company release notes.

"Because regulatory reviews are typically fluid and not definitive interactions between the sponsor and agency on individual elements of an application and related information, Amarin does not plan to update investors further on ongoing communications with regulatory authorities except with respect to potential updates regarding any change to the expected timing of the AdCom or the PDUFA date."

"Dawn of a New Era"

The REDUCE-IT study involved 8179 patients from 11 countries who were at elevated CV risk because of a previous CV event or diabetes with one additional risk factor, and increased triglyceride levels despite statin therapy. All participants were randomly allocated to 4 g of Vascepa daily or placebo.

The company announced topline results in September 2018, as reported by Medscape Medical News.

After a median follow-up of 4.9 years, there was an approximately 25% relative risk reduction in the primary end point of first occurrence of a major adverse cardiovascular event (MACE) — any one of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization — in the Vascepa group, which was highly significant (< .001), the company reported.

Final results of the REDUCE-IT trial were released last November at the American Heart Association (AHA) Scientific Sessions 2018 and simultaneously published online in the New England Journal of Medicine.

The final results showed "large consistent reductions on multiple endpoints and statistics which show that these results are extremely statistically significant and robust," lead investigator Deepak L. Bhatt, MD, Brigham and Women's Hospital, Boston, told theheart.org | Medscape Cardiology at that time.

"This is the dawn of a new era," Bhatt added, "as it opens up an entirely new avenue of prevention. It feels like a similar situation to that of the early statin trials in which large effects were seen across multiple endpoints and subgroups."

Discussant for the study at the AHA's late-breaking clinical trials session, Carl Orringer, MD, University of Miami, was equally impressed with the findings. "This is a seminal study," he commented to theheart.org | Medscape Cardiology .

The results of REDUCE-IT are "strikingly positive," said Orringer, with a 4.4% absolute reduction in MACE and a number needed to treat to prevent one event of just 21.

"If we just consider the hardest endpoints of CV death, MI, or stroke, the trial showed a 3.6% absolute risk reduction with a number need to treat of 28," Orringer noted. "We rarely see such large risk reductions, and these results are indicative of a highly effective intervention."

John Thero, president and chief executive officer of Amarin, said the company looks "forward to the planned advisory committee meeting as an opportunity to highlight the landmark REDUCE-IT data and the important role we expect Vascepa should play in the treatment of cardiovascular disease in appropriate patients."

Thero said the company will "continue to work collaboratively with the FDA on the pending REDUCE-IT sNDA while we prepare for a robust launch of REDUCE-IT data assuming approval of Vascepa before the end of 2019 for a cardiovascular risk reduction indication based on REDUCE-IT."


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