CETP inhibitor meets primary endpoint in CV outcome study
The REVEAL (Randomized EValuation of the Effects of Anacetrapib through Lipid modification) outcomes study of anacetrapib met its primary endpoint, significantly reducing major coronary events (defined as the composite of coronary death, myocardial infarction, and coronary revascularization) compared to placebo in patients at risk for cardiac events who are already receiving an effective LDL-C lowering regimen.
Anacetrapib is an investigational cholesteryl ester transfer protein (CETP) inhibitor. The REVEAL study is a randomized, double-blind placebo-controlled clinical trial to assess the efficacy and safety of adding anacetrapib (100 mg once daily) to effective LDL-lowering treatment with atorvastatin for a median duration of at least 4 years among approximately 30,000 patients at high risk of cardiovascular events. Based on a major coronary event rate of 1.8% per annum and median follow-up of 4 years, the trial of 30,000 participants would have 88% power at 2-tailed P<0.01 to detect a 15% relative risk reduction.
The safety profile of anacetrapib in the early analysis was generally consistent with that demonstrated in previous studies of the drug, including accumulation of anacetrapib in adipose tissue, as has been previously reported.
Pharmacological CETP inhibition yields increases in HDL-c and apolipoprotein A1, as well as decreases in LDL-c and apolipoprotein B. The extent to which this occurs varies per CETP inhibitor. To date, CETP inhibitors had not demonstrated benefit in CV outcome trials.
Anacetrapib is an orally active CETP inhibitor that increased HDL-c by 138% and apolipoprotein A1 by 45% in the placebo-controlled DEFINE trial (n=1600, follow-up: 18 months) and lowered LDL-c, apolipoprotein B and lipoprotein(a) by 40%, 21% and 36%, respectively.
Merck plans to review the results of the trial with external experts, and will consider whether to file new drug applications with the U.S. Food and Drug Administration (FDA) and other regulatory agencies. The results of the REVEAL study will be presented at the European Society of Cardiology meeting on Aug. 29, 2017.