New Indication Approval Sought for Icosapent Ethyl

Pharmaceutical developer Amarin Corporation has submitted a supplemental new drug application (sNDA) to the FDA seeking an expanded indication for icosapent ethyl (Vascepa) capsules.¹

The prescription drug is indicated for use with proper diet for lowering high levels of triglycerides in adults.²

Icosapent ethyl capsules are a single-molecule prescription product consisting of the omega-3 acid commonly known as EPA in ethyl-ester form. Icosapent ethyl 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 from degradation.¹

The sNDA to expand indication for Icosapent ethyl is based on the landmark REDUCE-I cardiovascular (CV) outcomes study, according to Amarin.

Study data suggest that the drug helps reduce the risk of major adverse CV events (MACE) in certain patients.¹

Company officials are operating under the assumption that the sNDA will be reviewed on a standard review clock of 10 months, according to a statement issued by Amarin.

Amarin tentatively expects a Prescription Drug User Fee Act date near the end of January 2020, based on the review timing, they said in the statement.¹

"This submission is another step forward toward our goal to help address the risk of cardiovascular disease," John F. Thero, chief executive officer and president of Amarin, said in a statement.¹

"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," he said. "This unprecedented result beyond cholesterol management presents an important new preventative care opportunity for millions of patients."

The sNDA submission includes data from more than 35,000 patient years of study from REDUCE-IT, which was completed in 2018.¹

REDUCE-IT relied on the CV outcomes of 8179 enrolled patients and was the first multinational CV outcomes study that evaluated the effect of prescription pure EPA therapy as an add-on to statins in patients with high CV risk who, despite stable statin therapy, had elevated triglyceride levels (at least 135 mg/dL). A large portion of the male and female patients enrolled in this outcomes study were diagnosed with type 2 diabetes.¹

In REDUCE-IT, icosapent ethyl displayed a 25% relative risk reduction compared with the placebo in the first occurrence of a major adverse CV event (MACE) in the intent to-treat population consisting of a composite of coronary revascularization (procedures such as bypass and stents), CV death, nonfatal heart attack or myocardial infarction (MI), nonfatal stroke, and unstable angina requiring hospitalization.

For total CV events, icosapent ethyl provided a statistically significant 30% risk reduction compared with the placebo in the statin-treated patient population included in the study, according to Amarin.¹

REDUCE-IT was performed under a special protocol assessment with the FDA. In the study, adverse events occurring with icosapent ethyl use at greater than 5% and greater than the placebo were: peripheral edema (6.5% icosapent ethyl, versus 5.0%), though there was no increase in the rate of heart failure in icosapent ethyl patients; constipation (5.3% icosapent ethyl, versus 3.6%), though mineral oil, as used as a placebo, is known to lower constipation; and atrial fibrillation (5.3% icosapent ethyl, versus 3.9%), though there were reductions in rates of cardiac arrest, sudden death and MIs observed in icosapent ethyl patients.¹

References

• Amarin submits supplemental new drug application (SNDA) to US FDA seeking new indication for Vascepa (icosapent ethyl) to reduce the risk of major adverse cardiovascular events based on landmark REDUCE-IT™ cardiovascular outcomes study [news release]. Bedminster, NJ; March 28, 2019: Amarin website. investor.amarincorp.com/news-releases/news-release-details/amarin-submits-supplemental-new-drug-application-snda-us-fda. Accessed March 29, 2019.
• Amarin Corp. About Vascepa. Amarin website. vascepa.com/about-vascepa. Updated 2019. Accessed March 29, 2019.