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Eicosapentaenoic Acid (EPA) Combined with Widely Used Statins Significantly Reduced Lipid Oxidation in Model Membranes

April 1, 2022 7:00 AM

DUBLIN, Ireland and BRIDGEWATER, N.J., April 01, 2022 (GLOBE NEWSWIRE) -- 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.


1 Witztum JL TheLancet.1994;344:793-7952 Chisolm GM and Steinberg D. FreeRadicBiolMed. 2000; 28:1815-18263 Jacob RF and Mason RP. JBiolChem. 2005; 280:39380-393874 Ehara S et al. Circulation. 2001; 103:1955-19605 Walter MF et al. JAmCollCardiol. 2008; 51:1196-12026 Walter MF et al. JAmCollCardiol. 2004; 44:1996-20027 Holvoet P et al. Diabetes. 2004; 53:1068-10738 Mason RP et al. Biomed Pharmacother. 2018; 103:1231-1237

About Amarin Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. From our foundation in scientific research to our focus on clinical trials, and now our commercial expansion, we are evolving and growing rapidly. Amarin has offices in Bridgewater, New Jersey in the United States, Dublin in Ireland, Zug in Switzerland, and other countries in Europe as well as commercial partners and suppliers around the world. We are committed to increasing the scientific understanding of the cardiovascular risk that persists beyond traditional therapies and advancing the treatment of that risk.

About VASCEPA® (icosapent ethyl) CapsulesVASCEPA (icosapent ethyl) capsules are the first-and-only prescription treatment approved by the U.S. Food and Drug Administration (FDA) comprised solely of the active ingredient, icosapent ethyl (IPE), a unique form of eicosapentaenoic acid. VASCEPA was launched in the United States in January 2020 as the first and only drug approved by the U.S. FDA for treatment of the studied high-risk patients with persistent cardiovascular risk after statin therapy. VASCEPA was initially launched in the United States in 2013 based on the drug’s initial FDA approved indication for use as an adjunct therapy to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. Since launch, VASCEPA has been prescribed over ten million times. VASCEPA is covered by most major medical insurance plans. In addition to the United States, VASCEPA is approved and sold in Canada, Lebanon and the United Arab Emirates. In Europe, in March 2021 marketing authorization was granted to icosapent ethyl in the European Union for the reduction of risk of cardiovascular events in patients at high cardiovascular risk, under the brand name VAZKEPA.

Indications and Limitation of Use (in the United States)

VASCEPA is indicated:

The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.

Important Safety Information


Forward-Looking StatementsThis press release contains forward-looking statements which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding any new potential clinical impact of VASCEPA, whether alone and/or in a combination product, the outcomes or impact of any specific new or ongoing clinical trials or studies, clinical, scientific, and/or statistical significance of any data generated in new or ongoing clinical trials or studies and general statements about the safety and effectiveness of VASCEPA and/or a potential combination product with VASCEPA and any specific statin. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties, including that Amarin's ability to effectively develop, obtain regulatory approval, commercialize and maintain or grow its market share of VASCEPA and/or any combination product which will depend in part on Amarin’s ability to continue to effectively finance its business and development efforts; to successfully achieve regulatory and marketing approvals in geographies in the United States and outside the U.S., which may rely on certain efforts of third parties; to maintain effective education, marketing and sales activities to achieve broad market acceptance; to receive adequate levels of reimbursement from third-party payers; to develop and maintain a consistent source of commercial supply at a competitive price; to comply with legal and regulatory requirements in connection with its sales and promotional efforts; and to secure, maintain and defend its patent protection for VASCEPA and/or any combination product. A further list and description of these risks, uncertainties and other risks associated with an investment in Amarin can be found in Amarin's filings with the U.S. Securities and Exchange Commission, including Amarin’s annual report on Form 10-K for the full year ended 2021. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. Amarin undertakes no obligation to update or revise the information contained in its forward-looking statements, whether as a result of new information, future events or circumstances or otherwise. Amarin’s forward-looking statements do not reflect the potential impact of significant transactions the company may enter into, such as mergers, acquisitions, dispositions, joint ventures or any material agreements that Amarin may enter into, amend or terminate. Availability of Other Information About Amarin communicates with its investors and the public using the company website (www.amarincorp.com) and the investor relations website (investor.amarincorp.com), including but not limited to investor presentations, Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Amarin posts on these channels and websites could be deemed to be material information. As a result, Amarin encourages investors, the media and others interested in Amarin to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Amarin’s investor relations website and may include social media channels. The contents of Amarin’s website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.Amarin Contact Information Investor Inquiries: Investor Relations Amarin Corporation plc [email protected] (investor inquiries)

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Source: Amarin Corporation plc


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