Amarin Corporation plc announced that the U.S. Food and Drug Administration (FDA) has approved a new indication and label expansion for VASCEPA (icosapent ethyl) capsules. After more than a decade of development and testing, VASCEPA is now the first and only drug approved by the FDA “as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥150 mg/dL) and established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular disease.” It is estimated that millions of high-risk patients in the United States could benefit from this one-of-a-kind prescription therapy.
“We at Amarin are excited and gratified to now have the opportunity to introduce VASCEPA as a new FDA-approved treatment option to reduce the persistent cardiovascular risk that many patients face despite use of statins with other contemporary standard-of-care therapies,” said John F. Thero, president and chief executive officer of Amarin. “We aim to help millions of high-risk patients, including statin-treated patients and statin-intolerant patients. For the first time, physicians, patients and payers have an FDA-approved treatment option beyond cholesterol lowering that has been demonstrated to significantly reduce major adverse cardiovascular events when used on top of a statin. We look forward to helping educate physicians and patients on the value of VASCEPA. The expanded indication and related clinical study labeling is broadly worded, informative on the many effects of VASCEPA and will empower physicians with critical information to help them apply their clinical judgment in addressing cardiovascular disease risk for patients in need.”
Amarin reaffirmed its intention to promptly launch VASCEPA in the United States for this important new preventative care indication. As previously disclosed, Amarin doubled the size of its sales force near the beginning of 2019 and is on track to double the size of its sales force again to a total of 800 sales representatives near the beginning of 2020.
“The FDA approval of icosapent ethyl as an addition to statin therapy to reduce the risk of cardiovascular events is a major milestone in cardiovascular prevention,” said Deepak L. Bhatt, M.D., M.P.H., executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, professor of medicine at Harvard Medical School, and lead investigator of the REDUCE-IT study which served as the basis for the supplemental New Drug Application to the FDA for VASCEPA. “Nothing this significant has happened in the world of cardiovascular prevention since the introduction of statins nearly three decades ago. Many patients stand to benefit from this historic advance in care.”
In the global REDUCE-IT cardiovascular outcomes study, approximately 28 percent of patients in the control arm treated with statins and other contemporary therapy but not treated with VASCEPA experienced a major adverse cardiovascular event (MACE), defined as the first occurrence of either myocardial infarction (heart attack), stroke, coronary revascularization, unstable angina requiring hospitalization or cardiovascular death. As evidenced by this MACE occurrence, there is a group of patients who, despite controlling their cholesterol on statin therapy, continue to have a high need for additional preventative cardiovascular care. For those adult patients in this group who have elevated triglycerides (TG) ≥150 mg/dL and established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease, VASCEPA is the first drug approved to help reduce this persistent cardiovascular risk. In a published exploratory analysis of the REDUCE-IT study, examining total (first and subsequent) cardiovascular events over a period of approximately five years, patients taking VASCEPA on average experienced one fewer MACE per six patients studied, representing a 30 percent risk reduction in total MACE compared to placebo.
The overall rates of adverse events and serious adverse events in the 5-year REDUCE-IT study were similar between VASCEPA-treated patients and placebo-treated patients. As reflected in VASCEPA’s expanded label and described below, VASCEPA has been associated with increased risks of bleeding and atrial fibrillation/flutter, the latter being more prevalent in patients with a previous history of atrial fibrillation or flutter. It is recommended that patients taking VASCEPA and concomitant anticoagulants and/or anti-platelet agents for bleeding be monitored. Also noted in the REDUCE-IT study is that patients for whom bleeding and/or atrial fibrillation/flutter were reported appeared to obtain a similar reduction in MACE as patients not reporting such adverse events. Such findings are consistent with published results of the study, which noted that the increased rates of such adverse events were low, notably lower than the reduction in MACE.
Recurrent event analyses were conducted of the total primary endpoint events and total key secondary endpoints in REDUCE-IT using a series of statistical models and published in the Journal of the American College of Cardiology. These analyses are not in FDA labeling, were tertiary or exploratory endpoints; most of the models used were prespecified and one was post hoc. Each recurrent event statistical model has inherent strengths and weaknesses, with no single model considered definitive or outperforming the other models, and this is an evolving field of science. Nonetheless, results from these analyses are consistent across the various models; they also are consistent with the original primary and secondary endpoint results. Together, the REDUCE-IT recurrent event analyses and the original primary and key secondary endpoint analyses support the robustness of the clinical benefit of VASCEPA therapy in reducing cardiovascular risk.