SAFETY AND EFFICACY OF OBICETRAPIB IN PATIENTS AT HIGH CARDIOVASCULAR RISK

Therapeutic Area

Pharmacologic Therapy

Background

Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that lowers low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib has not been fully characterized in patients at high risk of cardiovascular events.

Methods

BROADWAY 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.

Results

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 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.

Conclusions

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.