sNDA Submitted for Icosapent Ethyl for MACE Reduction Indication

Amarin Corporation plc has submitted a supplemental New Drug Application (NDA) to the US Food and Drug Administration (FDA) for icosapent ethyl (Vascepa) for an expanded indication. The application seeks a new indication to reduce the risk of major adverse cardiovascular events and is based on results from the REDUCE-IT cardiovascular outcomes study.

"The REDUCE-IT results support that approximately 1 fewer major cardiovascular adverse event would occur on average for every 6 patients treated with Vascepa for 5 years on top of statin therapy compared to placebo,” said John F. Thero, president and chief executive officer of Amarin. “This unprecedented result beyond cholesterol management presents an important new preventative care opportunity for millions of patients."

The REDUCE-IT trial compared icosapent ethyl to placebo in 8179 patients treated with statins who had LDL-C between 41-100 mg/dL. Participants received 4 grams per day of icosapent ethyl or placebo, and the median follow-up time was 4.9 years.

The trial met its primary endpoint, providing a 25% risk reduction in major adverse cardiovascular events (P <.001). The composite endpoint included 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.

Michael Miller, MD, a REDUCE-IT investigator and director of the Center for Preventive Cardiology, University of Maryland Medical Center, Baltimore, MD, spoke with MD Magazine® at the American Heart Association’s Scientific Sessions 2018 in Chicago, IL.

“REDUCE-IT now shows not only a 25% reduction in risk of future events, but also a 20% lowering of cardiovascular death,” Miller told MD Mag. “In this space—in the statin era&mdash;this is the first study to show a benefit on cardiovascular death on top of the 25% reduction in MACE events.”

Additionally, icosapent ethyl provided a significant 30% risk reduction in total (first and subsequent) cardiovascular events compared to placebo.

The adverse events that occurred at >5% with icosapent ethyl and greater than placebo were peripheral edema (6.5% vs 5.0%), constipation (5.3% vs 3.6%), and atrial fibrillation (5.3% vs 3.9%). However, the placebo, mineral oil, is known to lower constipation.

Icosapent ethyl was originally approved by the FDA in 2012 and is currently indicated as a supplement to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia.

"This submission is another step forward toward our goal to help address the risk of cardiovascular disease," added Thero.

The company anticipates that the FDA will review the application on a standard 10-month timeline, with a PDUFA date at the end of January 2020, and that there will be an Advisory Committee meeting. However, there has not yet been confirmation from the FDA on those points.