Safety and efficacy of obicetrapib in patients at high cardiovascular risk.

Abstract

Background: Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that lowers lowdensity lipoprotein (LDL) cholesterol levels. Purpose(s): The efficacy and safety of obicetrapib have not been fully characterized in patients at high risk of cardiovascular events. Method(s): BROADWAY (NCT05142722) enrolled 2530 patients with familial hypercholesterolemia (FH) or a history of atherosclerotic cardiovascular disease (ASCVD), treated with maximally tolerated lipid lowering therapy. Patients with either LDL cholesterol 3100 mg/deciliter and/ or non-high-density lipoprotein (non-HDL) cholesterol 3130 mg/deciliter or LDL cholesterol 55-100 mg/deciliter and/or non-HDL cholesterol 85-130 mg/deciliter with at least one additional cardiovascular risk factor were randomized (2:1) to obicetrapib 10 mg or matching placebo daily for 365 days. The primary endpoint was the percent change from baseline to Day 84 in LDL cholesterol. Result(s): Patients (mean age 65 years, female 33%, White race 74%, ASCVD 89%, FH 16%, statin use 90%) had a mean baseline LDL cholesterol level of 98 mg/deciliter. The difference between placebo and obicetrapib for the change in LDL cholesterol was -32.7% (95% confidence interval [CI] -35.8, -29.5), P<0.0001. The percent change from baseline in 12 ABSTRACT LDL cholesterol at day 84 was +2.7% (95% CI -0.4, 5.8) with placebo and -29.9% (95% CI -32.1, -27.8) with obicetrapib. The incidence of adverse events was similar across treatment groups. Conclusion(s): Obicetrapib was well tolerated and produced placebo-adjusted LDL cholesterol reductions of 32.7% in patients at high risk of cardiovascular events with elevated lipid levels despite treatment with maximally tolerated lipid-lowering therapy.