Amarin Corporation plc (NASDAQ: AMRN) today announced in vitro research results suggesting that Eicosapentaenoic Acid (EPA), in combination with widely prescribed statins (often referred to under brand names LIPITOR® and CRESTOR®), contributed to a reduction in lipid oxidation in membranes in a manner that may be enhanced with the use of these statins.

Amarin’s VASCEPA®/VAZKEPA® (icosapent ethyl) is the highly purified, prescription form of the ethyl ester of EPA. The research results will be presented on behalf of all authors by Preston Mason, Ph.D., of Brigham & Women’s Hospital and Elucida Research, LLC, during a poster session at the American College of Cardiology’s 71st Annual Scientific Session in Washington, DC, on Saturday, April 2nd. The experiment was conducted with financial support from Amarin and Elucida Research.

The oxidation of lipids in vascular cell membranes can be an important factor in heart disease and risk of an adverse cardiovascular event, as it contributes to inflammation, endothelial dysfunction, and cholesterol domain and foam cell formation during atherogenesis,1-3 as well as to circulating levels of oxidized LDL, which correlate with acute coronary syndromes and increased risk for ischemic events (such as a heart attack or stroke) and metabolic disease.4-7

In this experiment, the dose-dependent effects of EPA at concentrations of 5 and 10 micromolar (µM) on rates of lipid oxidation were measured by iodometric approaches with fixed concentrations of ATM and rosuva (1.0 µM) under conditions of autoxidation for 96 hr. After 96 h, control (untreated) membranes underwent significant oxidation with lipid peroxide (LOOH) levels reaching 2049 ± 286 µM.

EPA was found to have significantly reduced lipid oxidation in a dose-dependent fashion in the absence and presence of either ATM or rosuva. The combination of EPA/ATM and EPA/rosuva reduced lipid oxidation by 86 and 75%, respectively (p<0.001). The antioxidant activity of the EPA/ATM combination was more potent than EPA/rosuva by 59% (p<0.01) due, in part, to the more potent activity of ATM separately, which reduced LOOH levels 72% compared to rosuva alone (p<0.001).

These results are in line with prior experiments which suggested that treatment with EPA inhibited endothelial dysfunction following challenge with oxidized LDL and high glucose levels in a manner that may be enhanced with a high-intensity statin.8 The authors posit that this may be due to increased antioxidant activity achieved via the combination of EPA with statins due to complementary physico-chemical properties.

“The message that emerged for us from these in vitro study results was that, while statins and EPA can work independently to reduce lipid oxidation which can contribute to cardiovascular risk, they might work even better together,” said Dr. Mason. “This is an important finding with potential implications in particular for those facing persistent, elevated cardiovascular risk or who have had a prior event, as they may need more potent solutions than the standard of care can provide.”

“These findings are another compelling piece of evidence in line with our beliefs regarding the potential for increased benefit to appropriate high-risk patients from VASCEPA/VAZKEPA in combination with statins, consistent with the results from the REDUCE-IT® trial, and supports Amarin’s decision to focus on research and development efforts toward the possible development of a combination product,” said Karim Mikhail, Amarin’s president and chief executive officer.

References

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