WASHINGTON -- Icosapent ethyl, the prescription fish-oil product sold as Vascepa, may now be marketed for in adults with triglyceride levels of 150 mg/dL or higher, the FDA said late Friday.
The approval is restricted to people with established cardiovascular disease (CVD) or diabetes plus at least two other risk factors for CVD, and who are already taking maximally tolerated doses of statins, the agency noted.
An FDA advisory committee voted unanimously last month to recommend the approval, largely on the basis of the so-called REDUCE-IT trial that demonstrated a 25% reduction in total CV events after some 5 years of follow-up.
REDUCE-IT was a double-blind trial of more than 8,000 people who had elevated triglyceride levels despite at least 4 weeks of statin use. The cohort was randomized to icosapent ethyl or mineral-oil placebo on top of their statins.
Along with the primary endpoint (combined CV death, non-fatal MI, non-fatal stroke, coronary revascularization, and unstable angina), secondary endpoints such as death alone pointed to an advantage with icosapent ethyl.
Atrial fibrillation and bleeding were increased with use of the proprietary fish oil, though last month's FDA panelists said these events do not negate the product's cardiovascular benefit.
Critics of the trial have also highlighted unexpected biomarker changes in the placebo arm and suggested that mineral oil interacted with statin absorption to give icosapent ethyl the upper hand in clinical outcomes.
The expanded indication is the brass ring for Amarin Pharma, which has been seeking this approval for years. The company got into hot water with the FDA after its representatives began talking with physicians about research results suggesting such a risk reduction; the company then , with the agency eventually conceding defeat. But Amarin promised to continue with REDUCE-IT and to seek formal FDA approval for the indication.
Icosapent ethyl was originally approved in 2012 with an indication of triglyceride lowering, with no mention of clinical effects.
How icosapent ethyl confers its clinical benefit remains elusive, as it appears to be separate from triglyceride-lowering or other biomarker-affiliated mechanisms. The recent EVAPORATE study suggested that the agent slows down plaque progression.