November 24, 2011 (Orlando, Florida) — Further results from the two Phase 3 trials of the omega-3 fatty acid product ethyl eicosapentaenoic acid (EPA) (AMR101, Amarin), which showed the agent reduced triglycerides without increasing low-density lipoprotein (LDL) and also reduced the number of atherogenic particles, were presented last week at the American Heart Association 2011 Scientific Sessions.
The results of the two trials--ANCHOR and MARINE--have previously been reported by the company during conference calls. The main results of the MARINE study--which showed a reduction in triglycerides without an increase in LDL--were also reported earlier this year at the National Lipid Association (NLA) 2011 Scientific Sessions and published in September in the American Journal of Cardiology .
Latest results from the MARINE trial, presented at the AHA meeting by Dr Harold Bays (Louisville Metabolic and Atherosclerosis Research Center, KY), showed that that AMR101 4 g/day significantly reduced the number of large VLDL, total LDL, and small LDL particles, and significantly reduced VLDL particle size.
Bays commented to heartwire : "While these changes have not been proven to reduce atherogenic risk, it is widely believed that they should do so." He added that "the reduction in LDL particles is novel among omega-3 therapies and may correlate to the lack of LDL increase observed with AMR101."
AMR101 differs from currently available omega-3 products (which contain both EPA and docosahexaenoic acid [DHA]) in that it is the ethyl ester of EPA. The key selling point of AMR101 appears to be that it lowers triglycerides without the modest increase in LDL levels seen with other omega-3 products.
Presenting the ANCHOR results, Dr Christie Ballantyne (Methodist DeBakey Heart and Vascular Center, Houston, TX) explained that the number of individuals with high triglycerides is rising sharply with the increasing prevalence of obesity and diabetes.
In the ANCHOR study, 702 statin-treated patients with well-controlled LDL (median 83 mg/dL) and elevated triglycerides (median 259 mg/dL) were randomized to AMR101 (2 or 4 g/day) or placebo.
Results showed that AMR101 2 and 4 g significantly reduced median triglyceride levels by 10% and 21%, respectively, from baseline.
Change in Lipoprotein Levels From Baseline
|Non HDL-cholesterol, %||–5.5||–13.6|
|Apo B, %||–3.8||–9.3|
Ballantyne said AM101 showed a greater effect in patients on higher doses of statins, and the greatest effect on triglycerides occurred in patients with the highest triglyceride levels at baseline.
The 4-g group also showed significant reductions in lipoprotein phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP).
Ballantyne reported that adverse events were similar across treatment groups, with five discontinuations in the AMR101 4-g group, eight in the 2-g group, and 12 in the placebo group. There were no significant changes in fasting blood glucose, glycosylated hemoglobin, vital signs, ECGs, or liver or kidney function with either AMR101 dose.
He also said that the fishy taste that occurs with high doses of other omega-3 products "doesn't seem to be a problem with this product." He added that the company is starting an outcomes trial, but is in talks with the FDA about approval of the agent based on the lipid-lowering data alone. He commented: "The FDA may consider approval as long as an outcomes trial is underway. I think this is because the omega-3s have proven safety. Practically no side effects have been seen with this product so far."
Commenting for heartwire , cochair of the ANCHOR session, Dr Amit Khera (UT Southwestern Medical Center, Dallas, TX) said AMR101 was "enticing." "Patients like omega-3 fatty acids. They see them as more natural products than other drugs. There are many OTC products available, but these mostly contain 3–400 mg of EPA/DHA so you would need 12 capsules to get to 4 g--the amount needed to lower triglycerides effectively."
Khera noted that there was already a high-dose prescription product available, omega-3-acid ethyl esters (Lovaza, GlaxoSmithKline), which could be said to be comparable to AMR101. "It contains 960 mg EPA/DHA, so you need four capsules daily, but it is associated with a modest increase in LDL when taken by patients with very high triglycerides. This does not seem to be the case with AMR101. The reduction in CRP and LpPLA2 is also enticing, but I’m not sure how clinically different it will be."
He added: "What these differences mean is hard to know, as there are no outcomes data. But I suppose if they cost the same, then I think people will use the Amarin product. But if it is much more expensive, then I'm not so sure."
Both Khera and his fellow cochair, Dr Melvyn Rubenfire (University of Michigan, Ann Arbor), said they thought Amarin may gain FDA approval for AMR101 based on the MARINE and ANCHOR studies. Rubenfire commented to heartwire : "I would not think an outcome study is necessary for FDA approval when lipids are the target, considering the very long safety record of Lovaza." Noting that the outcome trial planned has a five-year duration, he added: "It makes no sense to me to wait for that result when the indication is to target lipids as recommended by AHA/ACC/NLA guidelines. The clinical outcome study would be necessary to get FDA approval as indicated for clinical event reduction."
The MARINE and ANCHOR trials were sponsored by Amarin. Ballantyne is a consultant for and receives honoraria from Amarin. Bays has received research grants and served as an advisor to Amarin.
Heartwire from Medscape © 2011 Medscape, LLC
Cite this: Further Results Show Ethyl-EPA Reduces Atherogenic Particles - Medscape - Nov 28, 2011.