Date: 18-Dec-2019

US FDA approves Amarin's Vascepa to reduce cardiovascular risk

Amarin Corporation plc, a pharmaceutical company, announced that the US 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 revascularisation, and unstable angina requiring hospitalisation 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, MPH, 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. Despite current treatment options, in the United States, there is one stroke and one heart attack each occurring on average every 40 seconds, and one cardiovascular death occurring on average every 38 seconds, or, in aggregate one such cardiovascular event every 14 seconds. Cardiovascular disease costs in the United States are in excess of US$500 billion each year, making it the nation's most expensive disease. The number of cardiovascular deaths is also increasing, serving as the No. 1 cause of death for men and women in the United States. These facts point to an acute need for more innovation in the cardiovascular disease therapeutic area. Since statin therapy was introduced nearly three decades ago, healthcare professionals have sought effective preventative care treatment options to reduce persistent cardiovascular risk beyond management of cholesterol. Many potential solutions failed to show favorable effects in cardiovascular outcomes studies. The development of Vascepa included learnings from these failures and now Vascepa is the first and only drug to succeed in reducing that risk in the patient group included in the new Vascepa label. Recently, a health economics study conducted by an expert group presented at the American Heart Association 2019 Scientific Sessions showed that use of Vascepa offers potential cost savings for the overall healthcare system (i.e., the cost of Vascepa is offset by cost savings from reducing the occurrence of high-cost major adverse cardiovascular events). This rare finding follows conclusions from a separate independent drug pricing watchdog group that found Vascepa cost effective for cardiovascular risk reduction, a result seldom achieved in this organization's analyses. Based on the unprecedented results of the REDUCE-IT outcomes study, multiple professional societies have updated guidelines or issued advisories to incorporate icosapent ethyl, including the American Diabetes Association, the European Society of Cardiology, The European Atherosclerosis Association, and the National Lipid Association. The new indication for Vascepa is incremental to its indication for which it was initially FDA approved, as an adjunct to diet to reduce triglyceride levels in adult patients with severe (=500 mg/dL) hypertriglyceridemia. The effect of Vascepa on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. "In achieving this expanded indication, Amarin appreciates the FDA's guidance in the design and conduct of multiple clinical trials of Vascepa across the past decade and for its diligence in reviewing the results of these studies," said Steven Ketchum, Ph.D, senior vice president and president, research & development and chief scientific officer, Amarin. "Moreover, Amarin is grateful to the thousands of patients and clinical sites who participated in the extensive study of Vascepa, which exceeded 37,000 patient-years of study in the clinical development program. Amarin also thanks its dedicated employees and advisors who overcame many challenges to achieve this important life-saving accomplishment." Vascepa (icosapent ethyl) capsules are the first-and-only prescription treatment approved by the FDA comprised solely of the active ingredient, icosapent ethyl (IPE), a unique form of eicosapentaenoic acid. Vascepa was initially launched in the United States in 2013 based on the drug's initial FDA approved indication for use as an adjunct therapy to diet to reduce triglyceride levels in adult patients with severe (=500 mg/dL) hypertriglyceridemia. Since launch, Vascepa has been prescribed over eight million times and is covered by most major medical insurance plans. The new, cardiovascular risk indication for Vascepa was approved by the FDA in December 2019.