CardioExchange Archive

An FDA advisory panel today failed to recommend an expanded indication for Vascepa, the purified EPA fish-oil product from Amarin. Vascepa is currently indicated only for the relatively small number of people with severe hypertriglyceridemia (>500 mg/dL). The proposed new indication would have greatly expanded the patient population eligible to receive Vascepa to the 20% of the U.S. population who have elevated triglycerides (>200 mg/dL) and existing CV disease or who are at high risk for CV disease.

The supplemental new drug application (sNDA) for the indication was based on the ANCHOR trial, which showed that Vascepa lowered triglycerides in the target patient population. But the FDA review (available here) raised two troubling issues. The first problem concerned the performance of the mineral oil placebo used in the trial. An unusual 9% increase in LDL levels in the placebo group led the FDA and panel members to wonder whether the placebo was not really biologically inert. This made it difficult to assess the true effect on lipids of Vascepa. Panel members wrestled with this issue but ultimately concluded that the triglyceride-lowering effect of Vascepa was genuine, though difficult to measure precisely.

But the panel didn’t agree that the triglyceride-lowering effect of Vascepa would translate into a significant clinical benefit. In its review the FDA said that several trials in recent years with niacin and fibrates (ACCORD-Lipid, AIM- HIGH, and HPS2-THRIVE) had failed to demonstrate cardiovascular benefits in patients already taking statins. In a vote of 9-2, the advisory panel members said that they preferred to wait for the results of the large ongoing Vascepa outcomes trial,  REDUCE-IT, which has enrolled more than 6000 of an eventual 8000 patients. Amarin said the trial is expected to be completed in 2016.

Panel chairman Robert Smith summarized the committee’s viewpoint as uncertain, both as to the magnitude of the effect on triglycerides and to whether these changes would result in improvements in cardiovascular outcomes.

Panel member Ellen Seely agreed that Vascepa effectively reduced triglycerides in the study population but that there was no evidence for any effect on outcomes. Seely stated her concern that the “bar may now be too high” for small companies and this may stifle competition. Her decision was somewhat eased because physicians still retain “some flexibility” because Vascepa will remain on the market and can be prescribed off-label.

Some panel members worried about the potential confusion that would ensue if the expanded indication was granted and REDUCE-IT turned out to be negative.