SOURCE: Amarin Corp. Plc

Amarin

April 04, 2016 07:00 ET

New Clinical and Pre-Clinical Data Presented at American College of Cardiology Meeting on the Effect of EPA Therapy in Statin-Treated Patients and on Endothelial Function in Exploratory Studies

BEDMINSTER, NJ and DUBLIN, IRELAND--(Marketwired - April 04, 2016) -  Amarin Corporation plc (NASDAQ: AMRN) today announced two posters presented yesterday at the annual meeting of the American College of Cardiology (ACC). This research adds to the growing body of clinical and pre-clinical data relevant to the use of EPA with statins.

The first poster, "Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Statin-Treated Patients With Elevated Cardiovascular Risk and Very High Triglyceride Levels: Results From the MARINE Study," is an exploratory subgroup analysis of results from Amarin's MARINE trial of Vascepa® (icosapent ethyl) and observed that, compared to placebo in statin-treated patients with elevated cardiovascular risk and very high triglycerides (TGs), Vascepa administered at 4 g/day significantly lowered TGs and improved other parameters relevant to cardiovascular health without raising LDL ("bad") cholesterol. The MARINE study and this subgroup analysis were led by Harold Bays, MD, Medical Director and President, Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY.

The second poster, a pre-clinical study titled, "Eicosapentaenoic Acid and Atorvastatin Active Metabolite, Alone or in Combination, Reversed Glucose- and Oxidized LDL-Induced Endothelial Dysfunction Measured Ex Vivo in Rats," noted that, independently and in combination, EPA and the active metabolite of atorvastatin improved endothelial function measured in rat kidney sections. This pre-clinical research was led by R. Preston Mason, Ph.D., Department of Medicine, Division of Cardiology, Brigham & Women's Hospital, Harvard Medical School, and president and founder, Elucida Research LLC.

"The results of these two studies add to the growing body of clinical and pre-clinical data on the effects of EPA when combined with statins under the conditions studied," said Steven Ketchum, Ph.D., president of research and development and chief scientific officer at Amarin. "Amarin's REDUCE-IT trial, examining the effect of EPA therapy on top of statin therapy in at-risk patients with elevated triglycerides has reached target enrollment and will provide needed cardiovascular outcomes data for this important patient population."

About the Presented Research

Dr. Bays' analysis was based on a subgroup of the MARINE trial, a study designed to determine the effects of high-purity, prescription-grade icosapent ethyl (Vascepa) on patients with severe hypertriglyceridemia, including those who were also receiving statin therapy. The 12-week, double-blind, phase 3 MARINE trial included patients (n=229) with TGs between 500 mg/dL and 2000 mg/dL. Statin treatment was not mandated as part of the study's inclusion criteria, but was used as a stratification factor. The subgroup analysis presented at ACC examined the effects of icosapent ethyl 4 g/day on fasting plasma lipid and lipoprotein parameters in the subgroup of patients from MARINE receiving stable statin therapy, with or without ezetimibe, which represented approximately 25% of the MARINE patient population.

This MARINE subgroup analysis focused on a comparison between statin-treated subjects administered 4 g/day icosapent ethyl (n=20) versus placebo (n=18), showing that, compared to placebo, icosapent ethyl significantly reduced TGs (-65%; P=0.0001), non-high-density lipoprotein cholesterol (-29%; P=0.0094), total cholesterol (-25%; P=0.0045), very-low-density lipoprotein cholesterol (-46%; P=0.0185), and RLP-C (-57%; P=0.0198) and numerically (all P>0.05) reduced ApoB (-7%), oxLDL (-10%), and ApoC-III (-23%). The reductions seen in the study were not associated with a significant increase in LDL-C (-2%) or change in high-density lipoprotein cholesterol (+2%) (P>0.05 vs placebo). As with many subgroup analyses, a limitation of this analysis is the small sample size, but the results are nonetheless suggestive of complementary beneficial changes in lipid and lipoprotein parameters from the addition of icosapent ethyl to statin therapy beyond statin therapy alone.

Dr. Mason's exploratory study was designed to determine if a combination of EPA and the active metabolite of atorvastatin could improve endothelial cell function in rat kidney sections. Endothelial dysfunction, a condition where the inner lining of the blood vessels is unable to provide its normal function of vasodilation and vasoconstriction, is a precursor to cardiovascular disease. The reduction of the release of nitric oxide (NO), which allows blood vessels to function properly, is often accompanied by a concomitant increase in peroxynitrite (ONOO) and is the primary cause of endothelial dysfunction. Increases in NO and the ratio of NO/ ONOO, along with decreases in ONOO, are considered indicators of improved endothelial function.

This research tested the separate and combined effects of EPA and the active metabolite of atorvastatin in rat kidney sections exposed to oxidized LDL (oxLDL) and high glucose levels. The combination of EPA and atorvastatin active metabolite increased NO release by 298% (P<0.001), decreased the release of ONOOby 32% (P<0.05), and increased the NO/ONOO ratio from 0.26 to 1.51 (P<0.001). The researchers concluded that the combined effects of EPA and the active metabolite of atorvastatin on the release of nitric oxide (NO) and the NO/ONOO ratio were significantly greater than what was observed for the active metabolite of atorvastatin alone.

Amarin's clinical development program for Vascepa includes a trial known as REDUCE-IT, the first multinational cardiovascular outcomes study evaluating the benefit of high-dose EPA therapy as an add-on to statins in patients with high cardiovascular risk who, despite stable statin therapy, have elevated triglyceride levels. The company announced last week that it has achieved its target enrollment of 8,000 patients for the trial and that an interim analysis by the independent Data Monitoring Committee of the REDUCE-IT trial is expected within the next six months.

Additional information on MARINE, REDUCE-IT and Amarin's other clinical studies of Vascepa can be found at www.clinicaltrials.gov.

About VASCEPA ®  (icosapent ethyl) capsules

VASCEPA® (icosapent ethyl) capsules are a single-molecule prescription product consisting of 1 gram of the omega-3 acid commonly known as EPA in ethyl-ester form. Vascepa is not fish oil, but is derived from fish through a stringent and complex FDA-regulated manufacturing process designed to effectively eliminate impurities and isolate and protect the single molecule active ingredient. Vascepa is known in scientific literature as AMR101.

FDA-approved Indications and Usage

  • VASCEPA (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.
  • The effect of VASCEPA on the risk for pancreatitis and cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.

Important Safety Information for VASCEPA

  • VASCEPA is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to VASCEPA or any of its components.
  • Use with caution in patients with known  hypersensitivity to fish and/or shellfish.
  • The most common reported adverse reaction (incidence >2% and greater than placebo) was arthralgia (2.3% for  Vascepa, 1.0% for placebo). There was no reported adverse reaction >3% and greater than placebo.
  • Patients receiving treatment with VASCEPA and other drugs affecting coagulation (e.g., anti-platelet agents) should be monitored periodically.
  • In patients with hepatic impairment, monitor ALT and AST levels periodically during therapy.
  • Patients should be advised to swallow VASCEPA capsules whole; not to break open, crush, dissolve, or chew VASCEPA.
  • Adverse events and product complaints may be  reported by calling
     1-855-VASCEPA or the FDA at 1-800-FDA-1088.

FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.

Vascepa has been approved for use by the United States Food and Drug Administration (FDA) as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Vascepa is under various stages of development for potential use in other indications that have not been approved by the FDA. Nothing in this press release should be construed as promoting the use of Vascepa in any indication that has not been approved by the FDA. Additional study is needed to determine if the effects of EPA shown in the research featured in this press release would have clinically meaningful benefit.

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 a commitment to the ongoing REDUCE-IT cardiovascular outcomes study. Vascepa® (icosapent ethyl), Amarin's first FDA-approved product, is a highly-pure, EPA-only, omega-3 fatty acid product available by prescription. For more information about Vascepa, visit www.vascepa.com. 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, including statements about the potential clinical importance of the findings presented, and the timing of interim data analysis in the REDUCE-IT trial. 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 on biomarkers thought to be relevant in the treatment of cardiovascular disease and with research in rodents as it relates to the potential for clinically meaningful effects in the human body, research and development and clinical trial risk generally, including the risk that such study results may not be predictive of future results or replicated in study in humans and that studied parameters may not have clinically meaningful effect, study results could be delayed by many factors including reliance on the third parties in the independent Data Monitoring Committee. 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 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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