REDUCE-IT study shows Vascepa can provide a 30% risk reduction in total CV events

Amarin Corporation plc presented new data from its landmark cardiovascular outcomes study of its prescription therapy, Vascepa (icosapent ethyl), the REDUCE-IT study, showing that Vascepa provided a statistically significant 30% risk reduction in total (first and subsequent) cardiovascular events compared to placebo in the statin-treated patient population studied in REDUCE-IT. These data presented as a late-breaker presentation at the American College of Cardiology's (ACC) 68th Annual Scientific Session in New Orleans, LA, and published simultaneously in the Journal of the American College of Cardiology, extend the scope of consistent effects of Vascepa beyond a patient's first cardiovascular event to all subsequent cardiovascular events, including cardiovascular death.

In November 2018, groundbreaking primary results of the REDUCE-IT study were presented and published showing that Vascepa achieved the primary endpoint of the study demonstrating a statistically significant 25% placebo-controlled risk reduction in the first occurrence of major adverse cardiovascular events (MACE) as well as statistically significant relative risk reductions in each component of the MACE composite, consisting of cardiovascular death, heart attack, stroke, coronary revascularization and hospitalization for unstable angina. For the primary endpoint, a clinically impactful number needed to treat of 21 was reported. In the newly reported data, investigators led by the study's principal investigator, Deepak L. Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School, Executive Director of Interventional Cardiovascular Programs in the Heart and Vascular Center at Brigham and Women's Hospital, and the Principal Investigator and Steering Committee Chair for REDUCE-IT, evaluated patients' total cardiovascular events during the median study follow up of 4.9 years in REDUCE-IT. These analyses were tertiary or exploratory endpoints in REDUCE-IT. Total events included both a patient's first occurrence of MACE as well as all subsequent occurrences of MACE. Recurrent cardiovascular events are common in people who have already had a heart attack. Various studies have found a recurrence rate of close to 50% for any cardiovascular event or for subsequent coronary revascularization in the year after a heart attack, and up to 75% of patients have a recurrent event within 3 years.

Vascepa reduced total events, first and subsequent events, by 30% compared to placebo, reflecting that for every 1000 patients treated for 5 years with icosapent ethyl versus placebo approximately 159 MACE could be prevented with Vascepa, including prevention of approximately 12 cardiovascular deaths, 42 heart attacks (myocardial infarctions), 14 strokes, 76 coronary revascularizations and 16 episodes of hospitalization for unstable angina. There was also a 28% reduction of total events in the key secondary endpoint of 3-point MACE in the intent-to-treat population consisting of a composite of cardiovascular death, nonfatal heart attack and nonfatal stroke.

"This is an impressive degree of risk reduction," said Dr. Bhatt. "From a patient's perspective — and from my perspective as a physician — we care about repeat events and the risk of surviving a first stroke or heart attack only to go on to have a subsequent, and potentially fatal, event. The degree of benefit that this analysis reveals is quite large, especially considering that this is an additional layer of benefit on top of what statin and other therapies have already provided."

REDUCE-IT was a global study of 8,179 patients who, despite stable statin therapy, had elevated triglyceride levels (at least 135 mg/dL) and either documented cardiovascular disease or diabetes with other cardiovascular risk factors. Many patients with well-managed LDL-cholesterol remain at high risk for cardiovascular events. No therapy is currently approved to treat such residual cardiovascular risk in the population studied in REDUCE-IT and, prior to the successful results of Vascepa demonstrated in the study, no other therapy had demonstrated a 25% risk reduction compared to placebo on top of statin therapy in a major cardiovascular outcomes trial within the primary endpoint of any patient population. REDUCE-IT studied Vascepa 4 grams/day as compared to placebo.

Benefits of Vascepa with respect to total cardiovascular event reduction were shown to continue over time. The cardiovascular event curve for Vascepa visually separated from the placebo event curve at approximately year one and continued to separate throughout the remaining follow-up period. This relatively early and continued separation of total cardiovascular event rates is consistent with the primary events data (i.e., first occurrence data) from REDUCE-IT previously reported. The separation was significant with respect to the primary endpoint of first events and grows further over time for total cardiovascular events.

The relative risk reduction demonstrated by Vascepa in REDUCE-IT has implications for both patient health and the cost of healthcare. Cardiovascular disease is the number one cause of death in the United States and most of the world. In the U.S., there is one cardiovascular death every 38 seconds. Cardiovascular disease is the most expensive area of healthcare. Treating major adverse cardiovascular events is expensive both at the time of the event and often for years to follow. This cost is not only financial; it impacts patients through pain and suffering and loss of productivity. Preventing such cardiovascular events would be beneficial for patients, their families and for healthcare at-large. Amarin believes that reducing approximately 159 MACE per 1000 patients treated will position Vascepa well in pharmacoeconomic analyses planned to be conducted and reported in 2019.

See- Bhatt DL, Steg PG, Miller M, et al." Effects of Icosapent Ethyl on Total Ischemic Events – Further Insights from REDUCE-IT". J Am Coll Cardiol 2019. epub ahead of print. http://www.onlinejacc.org/content/early/2019/03/01/j.jacc.2019.02.032.