BROADWAY: obicetrapib lowers LDL-C by 29.9% versus 2.7% with placebo in 2,530 high-risk patients (N Engl J Med 2025)

Original title: Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk

N Engl J Med · 7 May 2025 · 9

Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, Navar AM, Nissen SE, Harada-Shiba M, Curcio DL, Neild A, Kling D et al.

The BROADWAY trial randomised 2,530 patients with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease, on maximum tolerated lipid-lowering therapy, 2:1 to obicetrapib 10 mg daily or placebo for 365 days (mean age 65, 34% female, mean baseline LDL-C 98 mg/dL). At the primary endpoint, day 84, LDL-C fell by a least-squares mean of 29.9% (95% CI, 27.8 to 32.1) with obicetrapib against 2.7% with placebo, a between-group difference of 32.6 percentage points (95% CI, 29.5 to 35.8, P < 0.001). Adverse event rates were similar between groups. The pivotal phase 3 registration trial establishing obicetrapib efficacy and safety in high-risk ASCVD and HeFH, funded by NewAmsterdam Pharma, registered as NCT05142722.

Original abstract

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

Methods: We conducted a multinational, randomized, placebo-controlled trial involving patients with heterozygous familial hypercholesterolemia or a history of atherosclerotic cardiovascular disease who were receiving maximum tolerated doses of lipid-lowering therapy. Patients with an LDL cholesterol level of 100 mg per deciliter or higher or a non-high-density lipoprotein (HDL) cholesterol level of 130 mg per deciliter or higher, as well as those with an LDL cholesterol level of 55 to 100 mg per deciliter or a non-HDL cholesterol level of 85 to 130 mg per deciliter and at least one additional cardiovascular risk factor, were eligible for inclusion. The patients were randomly assigned in a 2:1 ratio to receive either 10 mg of obicetrapib once daily or matching placebo for 365 days. The primary end point was the percent change in the LDL cholesterol level from baseline to day 84.

Results: A total of 2530 patients underwent randomization; 1686 patients were assigned to receive obicetrapib and 844 to receive placebo. The mean age of the patients was 65 years, 34% were women, and the mean baseline LDL cholesterol level was 98 mg per deciliter. The least-squares mean percent change from baseline to day 84 in the LDL cholesterol level was -29.9% (95% confidence interval [CI], -32.1 to -27.8) in the obicetrapib group, as compared with 2.7% (95% CI, -0.4 to 5.8) in the placebo group, for a between-group difference of -32.6 percentage points (95% CI, -35.8 to -29.5; P<0.001). The incidence of adverse events appeared to be similar in the two groups.

Conclusions: Among patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipid-lowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%. (Funded by NewAmsterdam Pharma; BROADWAY ClinicalTrials.gov number, NCT05142722.).

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.