The newly approved U.S. indication for icosapent ethyl (Vascepa; Amarin) is broadly in line with the entry criteria for the REDUCE-IT trial and includes a large high-risk primary-prevention population, as well as those with established cardiovascular disease (CVD). The drug, thus, could well be used by millions of patients in the United States alone.
The high-dose, purified eicosapentaenoic acid product was approved last week by the Food and Drug Administration for cardiovascular risk reduction among adults already taking maximally tolerated statins with triglyceride levels of 150 mg/dL or higher who have either established CVD or diabetes and two or more additional risk factors for CVD.
The approval is based largely on the REDUCE-IT trial’s finding of a 25% reduction in risk for major adverse cardiovascular events versus placebo. The FDA stated that the approval is the first for an agent with this specific indication.
Noting that it recognizes the need for additional medical treatments for CVD, the FDA says the new approval “will give patients with elevated triglycerides and other important risk factors, including heart disease, stroke, and diabetes, an adjunctive treatment option that can help decrease their risk of cardiovascular events.”
The drug was unanimously recommended for approval by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee last month. But while the committee all agreed on its use in patients with established CVD, which made up 70% of the REDUCE-IT population, they were divided on whether the indication should be extended to the high-risk primary-prevention population, who made up just 30% of patients in the study.
Nonetheless, the FDA has gone for a broad indication based on the whole REDUCE-IT population.
In a conference call following the approval, Steven Ketchum, PhD, chief scientific officer at Amarin, pointed out that the primary-prevention population stipulated in the new approval differed very slightly from the REDUCE-IT enrollment criteria.
The trial specified that patients with diabetes should be older than 50 with one other cardiovascular risk factor, whereas the approved population is for diabetes and two cardiovascular risk factors. But as these two risk factors are not specified, they could include age, cigarette smoking, hypertension or use of an antihypertensive agent, low HDL cholesterol, high C-reactive protein, body mass index above 25 kg/m2, renal dysfunction, retinopathy, albuminuria, or an ankle branchial index below 0.9, Dr. Ketchum said.
“So while the label asks for two other risk factors, one of these could be age; so we believe the label is actually slightly broader than the REDUCE-IT inclusion criteria, and doctors have been left with significant leeway to decide which risk factors to consider on top of diabetes.”
Deepak Bhatt, MD, the lead investigator of REDUCE-IT, described the Vascepa approval as “the most significant event in the field of cardiovascular prevention since the introduction of statins nearly 3 decades ago.”
He commended the FDA on “a very evidence-based, prescriber-friendly, and most importantly, patient-friendly label,” which he said was in line with guidelines from multiple professional societies that have already incorporated the REDUCE-IT findings for secondary prevention and diabetic primary prevention.
Dr. Bhatt, who is a professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, Boston, said the label essentially matches the REDUCE-IT population.
“The entry criteria for REDUCE-IT was fasting triglycerides greater than or equal to 150 mg/dL, with a 10% variance allowed (giving a minimum triglyceride value of 135 mg/dL). In actuality, we ended up with about 10% of the population with triglycerides between 100 and 150 mg/dL, and they had a similar degree of benefit as those with higher levels,” he reported.
“In the label, the 150 mg/dL does not specify fasting, and in fact many practices have moved away from fasting lipid measurements for the sake of patient comfort,” Dr. Bhatt added. “On average, nonfasting levels are about 50 mg/dL higher, so the label essentially mirrors those we studied, with the FDA applying good common sense and not being overly dogmatic about the exact wording of the trial inclusion criteria.”