The FDA's Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) unanimously concluded Thursday that Amarin Corp. plc provided sufficient evidence of efficacy and safety to support approval of fish oil-based Vascepa (icosapent ethyl) for an indication to reduce the risk of cardiovascular (CV) events in adults with elevated triglyceride levels (≥135 mg/dL) and other risk factors for CV disease.
The 16-0 vote followed a day's discussion about potential effects of mineral oil, about the proper age population and the value of labeling. EMDAC's conclusion is only an advisory, as the FDA makes the final decision. FDA representatives at the panel discussion noted the study provided convincing data and waived off most concerns about mineral oil's impact on LDL cholesterol levels and blood pressure.
The FDA's final decision on the label expansion is expected by the PDUFA date of Dec. 28.
"Today we moved an important step closer to potentially helping millions of patients who are at risk for cardiovascular events despite being on standard-of-care statin therapy," said John F. Thero, Amarin's president and CEO. "Vascepa is positioned to be the first approved treatment to reduce cardiovascular events in the group of at-risk patients studied in the landmark REDUCE-IT clinical trial. We appreciate both the opportunity to present these results and the committee's strong vote of confidence."
The discussion centered around the results of Amarin's phase III REDUCE-IT study. A lipid-regulating agent, Vascepa is an ethyl ester of eicosapentaenoic acid (EPA), an omega-3 fatty acid obtained from fish oil. The company noted that the FDA expected that REDUCE-IT results could satisfy uncertainty about Vascepa benefits on CV risk in that population, according to a Cortellis review of the adcom.
"I think it will benefit a substantial amount of the populace and will treat an unmet need," said Jack Yanovski, an EMDAC panel member, pediatric endocrinologist and chief of the Section on Growth and Obesity, Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Marvin Konstam, an EMDAC panel member and chief physician executive of the Cardiovascular Center at the Tufts Medical Center, said he thought the target patient population could possibly be enlarged.
"My inclination is toward approving the entire population but with a big asterisk," Konstam said. "I'd like to see the FDA do more work on this and look at the net clinical benefit in very hard ways, such as primary vs. secondary prevention."
James de Lemos, an EMDAC panel member and professor of medicine and distinguished chair in cardiology at the University of Texas Southwestern Medical Center, said Vascepa has great promise and he looks forward to a possible study for its use in primary prevention. Thomas Weber, another EMDAC panel member and associate professor of endocrinology, metabolism and nutrition at the Duke University Medical Center, agreed that Vascepa should be studied for primary prevention, though he added that the uncertainty about mineral oil "is the elephant in the room."
The company's stock was halted for Thursday's adcom. However, in the heaviest trading Amarin (NASDAQ:AMRN) has seen in nearly a year, its shares jumped more than 20%, hitting a high of $20.96 and ending Tuesday at $20.94. That's the best price the Dublin-based company has seen since August when its stock sank on the news that the FDA was convening an adcom a month and a half after the original Sept. 28 PDUFA date for the supplemental new drug application for the new indication of reducing CV risk in people with high triglyceride levels despite statin therapy. (See BioWorld, Aug. 12, 2019.)
The phase III REDUCE-IT (Reduction of Cardiovascular Events with EPA Intervention Trial) study of Vascepa (AMR-101) provided a 25% relative risk reduction compared to placebo in the first occurrence of a major adverse cardiovascular event and a statistically significant 30% risk reduction compared to placebo in the statin-treated patients in the intent-to-treat population.
The FDA first approved Vascepa on July 26, 2012, as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. Vascepa had sales of $228 million last year. It's expected to reach blockbuster status, with more than $1 billion in sales, by 2025, according to Cortellis.