U.S. FDA Grants Priority Review for Vascepa® (Icosapent Ethyl) Supplemental New Drug Application Seeking Cardiovascular Risk Reduction Indication

VASCEPA® (icosapent ethyl, or AMR101) capsules are a single-molecule prescription product consisting of highly purified EPA in ethyl-ester form. VASCEPA® 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 from degradation. Amarin has been issued multiple patents internationally based on the unique clinical profile of VASCEPA®, including the drug’s ability to lower triglyceride levels in relevant patient populations without raising LDL-cholesterol levels.

VASCEPA® is approved by the U.S. FDA to reduce triglyceride (TG) levels as an adjunct to diet in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. Based on the landmark REDUCE-IT cardiovascular outcomes study, Amarin submitted supplemental new drug application (sNDA) to FDA for the indication of residual cardiovascular risk reduction.

In May 29, 2019, Amarin’s NDA for VASCEPA® was accepted for filing and granted Priority Review designation by the U.S. FDA. The Prescription Drug User Fee Act (PDUFA) goal date assigned by the FDA for this sNDA is September 28, 2019. Because of the Priority Review designation, the timing of this PDUFA date is four months earlier than the anticipated standard ten-month review for applications.

Assuming FDA approval, VASCEPA® will be the first drug indicated to reduce residual cardiovascular risk in patients with statin-managed LDL-C cholesterol, but persistent elevated triglycerides, an important indicator of cardiovascular disease. This is a serious health challenge experienced by millions of people.

The FDA grants Priority Review designation to applications for drugs that, if approved, have the potential to offer significant improvements in the effectiveness and safety of the treatment of serious conditions when compared to standard applications. The unprecedented REDUCE-IT results will position Amarin to lead a transformative change in clinical practice for preventative treatment of cardiovascular disease. Amarin will significantly expand promotion of VASCEPA® following label expansion are being accelerated to reflect the upcoming PDUFA date.

sNDA Based on Landmark REDUCE-ITTM Trial

REDUCE-ITTM, a global study of 8,179 statin-treated adults with elevated CV risk, was performed based on a special protocol assessment (SPA) agreement with the FDA and completed in 2018. The sNDA for VASCEPA® is based on the landmark REDUCE-ITTM cardiovascular outcomes study, primary results of which were published in The New England Journal of Medicine in November 2018. Additional results and analysis of total recurrent events observed were subsequently published in the Journal of American College of Cardiology in March 2019.

In REDUCE-IT, VASCEPA® achieved the primary endpoint with a 25% relative risk reduction compared to placebo (95% confidence interval [CI], 0.68-0.83; p<0.001) in the first occurrence of a major adverse cardiovascular event (MACE) in the intent-to-treat population. In REDUCE-IT, MACE consisted of a composite of cardiovascular death, nonfatal myocardial infarction (MI or heart attack), nonfatal stroke, coronary revascularization (procedures such as stents and by-pass) and unstable angina requiring hospitalization.

As further evidence of the robustness of the REDUCE-IT results, VASCEPA® achieved the study’s key secondary endpoint with a 26% relative risk reduction (HR, 0.74; 95% CI, 0.65-0.83; p<0.001) in 3-point MACE in the intent-to-treat population consisting of a composite of cardiovascular death, nonfatal heart attack and nonfatal stroke. VASCEPA® also achieved seven other secondary endpoints in the pre-specified hierarchical order below the key secondary endpoint, including a 20% relative risk reduction in cardiovascular death compared to placebo (HR, 0.80; 95% CI, 0.66-0.98; p=0.03). REDUCE-IT, a global study of 8,179 statin-treated adults with elevated CV risk, was performed based on a special protocol assessment (SPA) agreement with the FDA.

Advances in Clinical Research of VASCEPA® in Mainland China

At present, millions of people in China are in the health threat of cardiovascular diseases. In order to bridge Chinese patients with cardiovascular diseases with globally revolutionary treatment options, Eddingpharm and Amarin reached an licensing agreement in February 2015 for Eddingpharm to develop, commercialize VASCEPA® in the territories of the mainland China, the Hong Kong, Macao Special Administrative Regions and Taiwan. Up to now, Eddingpharm has completed a pharmacokinetic (PK) study and a comparative PK analysis of race differences between Chinese and American healthy subjects in China.

Similar to the MARINE study in the US, ongoing VASCEPA® phase III clinical trial currently conducted by Eddingpharm in China is a multi-center, placebo-controlled, randomized, double-blind, 12-week study evaluating patients with severe hypertriglyceridemia (commonly named very high triglycerides or VHTG). The primary endpoint of this study is the median placebo-adjusted percentage change in TG levels from baseline to study end (week 12) in the treatment group and placebo group.

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