Ethyl-EPA Reduces Triglycerides in Mixed Dyslipidemia

April 25, 2011

April 20, 2011 (Dublin, Ireland and Mystic, Connecticut) — A semisynthetic derivative of omega-3 fatty acids, known as ethyl eicosapentaenoic acid (EPA) (AMR101, Amarin), significantly reduced triglyceride levels in patients with mixed dyslipidemia currently treated with statin therapy [1]. Among patients treated with the 4-g dose of ethyl-EPA, triglycerides decreased 21%, while a reduction of 10% occurred in patients treated with the 2-g dose.

Over the course of the 12-week, phase 3 clinical trial, known as the ANCHOR study, treatment with the ethyl-EPA did not increase LDL-cholesterol levels.

Presenting the top-line results of the trial during a conference call with analysts, investors, and the media--to comply with Securities and Exchange Commission regulations--Amarin company officials said they are pleased with the results, especially since no prescription omega-3 fatty acid is approved for the patient population studied in ANCHOR.

Speaking during the conference call, Dr Christie Ballantyne (Methodist DeBakey Heart and Vascular Center, Houston, TX) said that while statin therapy has been shown to be a safe and effective treatment for reducing the risk of coronary heart disease, there is a significant residual risk, even among patients who are treated to LDL-cholesterol targets. Focusing on other lipid and inflammatory markers, such as elevated triglycerides, apolipoprotein B (apoB), and non–HDL-cholesterol levels, can help identify these higher-risk patients.

"Treatment of these individuals with drugs that can be safely and effectively combined with statins could potentially result in a greater reduction of cardiovascular events than using statins alone," said Ballantyne.

Current therapies used to treat this patient population have limitations, he added, noting that niacin might cause flushing and elevations in blood glucose. Fibrates are questionable, especially when combined with statins, and existing omega-3 fatty acids might raise LDL-cholesterol levels, said Ballantyne. At present, prescription omega-3 fatty acids are approved for patients with very high triglyceride levels, such as those with levels >500 mg/dL.

The ANCHOR Trial

In ANCHOR, investigators randomized 702 patients with high triglyceride levels, those ranging from >200 mg/dL to <500 mg/dL, to placebo or 2 g or 4 g of ethyl-EPA. All patients were treated with statin therapy, including simvastatin, atorvastatin, and rosuvastatin, to an LDL cholesterol target of <100 mg/dL. At 12 weeks, treatment with both ethyl-EPA doses significantly reduced triglyceride levels, as well as reduced non-HDL cholesterol, apoB, lipoprotein phospholipase A2 (Lp-PLA2), and vLDL-cholesterol levels. Non-HDL cholesterol decreased 13.6% and 5.5% in the 4-g and 2-g doses, respectively.

"The reductions in triglycerides occurred even when AMR101 was combined with higher-potency statin regimens," noted Ballantyne. "In fact, we observed an increase in efficacy as the potency increased. This is an unexpected finding, which is encouraging for the use of AMR101 in high-risk patients, [since] we have been moving toward higher-potency statins."

As noted, LDL levels did not increase--the study was powered to assess noninferiority compared with placebo for any changes in LDL cholesterol--and, in fact, a superiority analysis showed the 4-g dose significantly reduced LDL cholesterol 6.2% compared with placebo, while there was a trend toward a 3.6% reduction with the 2-g dose.

The positive results of ANCHOR follow MARINE, another randomized, placebo-controlled trial that tested ethyl-EPA in 229 patients with triglyceride levels >500 mg/dL. Reported by heartwire in November 2010, the 2-g and 4-g doses reduced triglyceride levels 20% and 33%, respectively, and did so without increasing LDL-cholesterol levels. At present, neither ANCHOR nor MARINE have been published in a peer-reviewed journal and have not been presented at a medical meeting. The full results of MARINE will be presented at the upcoming National Lipid Association meeting in New York City in May, while no date has been set for publication or presentation of ANCHOR.

Amarin Corporation sponsored ANCHOR and MARINE.