FDA Approves EPA-Only Omega-3 PUFA Capsule for High TG


July 27, 2012

July 26, 2012 (Bedminster, New Jersey) — Late today the FDA approved a patented synthetic ethyl eicosapentaenoic acid (EPA), icosapent ethyl (Vascepa, formerly AMR101, Amarin) [1], for the treatment of hypertriglyceridemia. It should now become the market's second omega-3 polyunsaturated fatty acid (PUFA) preparation available only by prescription.

Vascepa is a purified marine-oil preparation of consisting of "not less than 96%" EPA, Amarin notes in its literature. It doesn't contain significant amounts of the other active omega-3 PUFA, docosahexaenoic acid (DHA), that is a major component of nonprescription fish-oil capsules and Lovaza (GlaxoSmithKline), which the FDA approved years ago.

There is evidence that EPA-only Vascepa may not elevate low-density-lipoprotein cholesterol (LDL-C), an undesirable effect long observed with the more familiar EPA/DHA omega-3 capsules, including Lovaza, as heartwire has reported. Clues to the possible mechanism behind that likely advantage came from a study last year suggesting that EPA-only omega-3 PUFA supplements had a less oxidizing effect on LDL than an EPA/DHA preparation.

Today's approval is based primarily on efficacy and safety data from the 12-week, phase 3 MARINE trial [2], in which triglyceride levels dropped while there were improvements in other relevant markers, including total cholesterol, apolipoprotein B (apo-B), lipoprotein-associated phospholipase A2 (Lp-PLA2), and high-sensitivity C-reactive protein (hs-CRP), all without significant increases in LDL-C.

Amarin says it is seeking separate FDA approval for using Vascepa in patients with high triglycerides who are on statins, the population explored in the ANCHOR trial, which heartwire reported last year and which was published online a week ago in the American Journal of Cardiology [3]. Of note in ANCHOR, the addition of Vascepa at 4 g/day to statins significantly lowered LDL-C (p=0.0067).

Neither MARINE nor ANCHOR looked at clinical outcomes.

Amarin recently launched another randomized trial, called Reduction of Cardiovascular Events with EPA--Intervention Trial (REDUCE-IT), in which Vascepa is added to statin therapy in "high-risk" patients with both elevated triglycerides and either coronary artery disease or CAD risk factors. Its primary end point includes cardiovascular events.

According to the company, REDUCE-IT is under way at about 300 international sites, primarily in the US, has a target enrollment of about 8000 patients, and is scheduled for completion in six years.