BEDMINSTER, NJ and DUBLIN, IRELAND–(March 04, 2015) – Amarin Corporation Plc (NASDAQ: AMRN), announced today the presentation of findings from a new in vitro study that the combination of eicosapentaenoic acid (EPA), an omega-3 fatty acid, and the active metabolite of atorvastatin (ATM) provided significantly increased nitric oxide (NO) bioavailability in an additive fashion. The study found that this effect was not observed with other triglyceride lowering agents (fenofibrate, niacin, or gemfibrozil) or the omega-3 fatty acid docosahexaenoic acid (DHA). The research was presented yesterday at a peer-reviewed poster session at the DEUEL Conference on Lipids in Monterey, California.

Endothelial cell dysfunction contributes to increased risk for atherosclerosis and heart disease and is characterized by reduced nitric oxide (NO) levels and increased production of the cytotoxic peroxynitrite anion that can lead to an inflammatory response in blood vessels.^(i),(ii) Endothelial cell dysfunction has been observed in patients with diabetes and is associated with other cardiovascular risk factors.^{(iii),(iv),(v)}

“With significant clinical research demonstrating the essential role of endothelial cell dysfunction in the development of atherosclerosis, it is critical that we explore therapeutic options to address the multiple risks in patients with high triglycerides,” said R. Preston Mason, Ph.D., Department of Medicine, Division of Cardiology, at the Harvard Medical School-Brigham and Women’s Hospital in Boston and lead author of the study. “The findings of this in vitro study clearly show the potential for an atheroprotective benefit with the combination of EPA and atorvastatin beyond therapeutic changes in lipid levels alone, and these results should support additional clinical research to better understand the exact mechanism for the observed effect.”

This study demonstrated that oxidative stress induced by oxidized LDL (oxLDL) decreased human umbilical vein endothelial cell (HUVEC) release of NO by 22% as compared to untreated cells. In HUVECs first exposed to oxLDL and then treated with EPA or ATM separately, NO release increased by 45% or 64%, respectively, while the EPA and ATM combination treatment significantly increased NO release by two-fold as compared to the oxLDL plus vehicle control. The NO/peroxynitrite (ONOO−) ratio, an indicator of normal endothelial cell function, significantly increased by approximately three-fold with the EPA and ATM treatment as compared to oxLDL plus vehicle control. An improvement in NO release over ATM alone was not observed with any of the other TG-lowering agents or with DHA in combination with the statin. These data suggest that EPA plus a statin such as atorvastatin may reverse endothelial cell dysfunction resulting from oxidative stress in a manner that is enhanced by their co-administration. More study is needed.

The study was supported by Amarin and led by a researcher from Brigham and Women’s Hospital in collaboration with investigators at Elucida Research in Beverly, MA and Ohio University in Athens, OH.

About Amarin

Amarin Corporation Plc is a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health. Amarin’s product development program leverages its extensive experience in lipid science and the potential therapeutic benefits of polyunsaturated fatty acids. Amarin’s clinical program includes commitment to an ongoing outcomes study. For more information about Amarin visit www.amarincorp.com.

Forward-looking statements

This press release contains forward-looking statements, including statements about the potential efficacy, safety and therapeutic benefits of EPA and atorvastatin and the clinical importance of certain parameters, the impact of such pharmaceutical intervention on such parameters and the potential for atheroprotective benefit. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development and clinical trials, including the risk that in vitro results may not be predictive of results in clinical trials or replicated and that studied lipid parameters may not have clinically meaningful effect. A 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 its most recent annual report on Form 10-K. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Amarin undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Availability of other information about Amarin

Investors and others should note that we communicate with our investors and the public using our company website (www.amarincorp.com), our investor relations website (http://www.amarincorp.com/investor-splash.html), including but not limited to investor presentations and investor FAQs, Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that we post on these channels and websites could be deemed to be material information. As a result, we encourage investors, the media, and others interested in Amarin to review the information that we post on these channels, including our investor relations website, on a regular basis. This list of channels may be updated from time to time on our investor relations website and may include social media channels. The contents of our website or these channels, or any other website that may be accessed from our website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

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⁽ⁱⁱⁱ⁾ Grattagliano I, Palmieri VO, Portincasa P, et al. J Nutr Biochem. 2008; 19:491-504.
^(iv) Kurioka S, Koshimura K, Murakami Y, et al. Endocr J. 2000; 47:77-81.
^(v) Mason RP, Kubant R, Jacob RF, et al. Am J Hypertens. 2009; 22:1160-1166.