FDA panel does not favor expanded indications for Vascepa

The FDA Endocrinologic and Metabolic Drugs Advisory Committee today voted against expanding indications for icosapent ethyl to include a wider patient population at this time.

The panel voted 9-2 against widening the indications based on results of the ANCHOR trial. Panel members said the available data show that icosapent ethyl (Vascepa, Amarin) reduces triglycerides, but do not convincingly demonstrate that it reduces CV risk. The committee said it awaits the results of the REDUCE-IT study, which will evaluate icosapent ethyl for the reduction of CV events in patients with hypertriglyceridemia who are taking a statin.

Clinical benefit uncertain

“The [CV] outcome benefit is uncertain based on the data presented,” committee chairman Robert J. Smith, MD, said when summarizing panel feedback to FDA staff.

Vascepa is an omega-3 fatty acid that was approved in July 2012 for the reduction of triglycerides in adults with severe hypertriglyceridemia. Amarin has applied for another indication for the drug, used in conjunction with a statin, to reduce triglycerides, non-HDL, apolipoprotein B, LDL, total cholesterol and very low density lipoprotein in adults with mixed dyslipidemia and CHD or a CHD risk equivalent.

The data on Vascepa in this patient population come from the ANCHOR trial, which tested the efficacy of icosapent ethyl for the reduction of high triglycerides without increasing LDL in 702 participants on statin background therapy. Those assigned 4 g Vascepa per day had a 21.5% decrease in triglycerides (P<.0001) and those assigned 2 g Vascepa per day had a 10.1% reduction in triglycerides (P=.0005) compared with those assigned mineral oil placebo.

However, while the ANCHOR trial data showed that participants assigned Vascepa received a benefit in terms of triglyceride levels and other lipid and lipoprotein indicators, it was not designed to demonstrate improved CV outcomes, and panel members said they were not willing to assume that improved lipid parameters would lead to improved CV outcomes.

“I’m not sure that we need more agents prescribed because we think maybe they’re going to work,” said panel member Peter W.F. Wilson, MD. “We should rely on what we know that works.”

Failed trials of other agents hurt cause

FDA staff and panel members said a factor working against expanding indications for Vascepa at this time is that between approval of the ANCHOR study design and now, other trials such as ACCORD, AIM-HIGH and HPS2-THRIVE produced results showing that agents added to statin therapy did not improve CV outcomes despite improving various lipid indicators.

“The scientific landscape has shifted dramatically in the last 4 to 5 years,” said panel member Brendan M. Everett, MD, MPH. “While I am optimistic that there could be substantial benefit for patients with CHD, I am wary of approving [an agent] without hard efficacy data.”

FDA staff and panel members also expressed concern about the mineral oil placebo used in ANCHOR. According to an FDA briefing document, the results “at least suggest the possibility that mineral oil may not be biologically inert” because “within-group changes in lipid parameters and biomarkers of inflammation from baseline to 12 weeks were highly statistically significant in the mineral oil placebo group (all P<.001).” It may not be clear whether the treatment effect was a result of icosapent ethyl lowering LDL or mineral oil raising LDL, according to the document.

The FDA is not required to follow the recommendations of its advisory panels, but it usually does. – by Erik Swain

For more information:

EMDAC Clinical Briefing Document. sNDA 202057/S-005.