Obicetrapib Lowers LDL-C by 36% in Familial Hypercholesterolaemia: BROOKLYN Trial Results
The BROOKLYN trial randomised 354 patients with heterozygous familial hypercholesterolaemia to obicetrapib 10 mg or placebo for 365 days. Obicetrapib achieved a placebo-adjusted LDL-C reduction of 36.3%, apoB reduction of 24.4%, and Lp(a) reduction of 45.9% at day 84. These results position CETP inhibition as a viable add-on therapy and underscore the central role of advanced lipid panel testing including apoB and Lp(a) quantification in monitoring treatment response.
The original study
Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial.
- Authors
- Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, et al.
- Journal
- Nature medicine
- Type
- Journal Article, Randomized Controlled Trial
- PMID
- 41760952
Original abstract
Most patients with heterozygous familial hypercholesterolemia fail to achieve adequate low-density lipoprotein (LDL) cholesterol lowering. Here we carried out a randomized trial to test the safety and efficacy of obicetrapib, a highly selective cholesteryl ester transfer protein inhibitor that lowers LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia and an LDL cholesterol level ≥70 mg dl-1 on maximally tolerated lipid-lowering therapy. The trial enrolled 354 patients (190 women, 164 men) with a mean LDL cholesterol level of 122 mg dl-1 (87% on statins) who were randomized (2:1) to receive obicetrapib 10 mg or placebo daily for 365 days. For the primary endpoint, the change in LDL cholesterol from baseline to day 84, obicetrapib treatment resulted in a placebo-adjusted change in LDL cholesterol of -36.3% (95% confidence interval -42.2% to -30.4%, P < 0.0001). In analyses of secondary endpoints at day 84, treatment with obicetrapib resulted in placebo-adjusted reductions in apolipoprotein B of -24.4%, non-HDL cholesterol of -34.5% and lipoprotein(a) of -45.9%, as well as a placebo-adjusted increase in high-density lipoprotein cholesterol of +138.7%. Obicetrapib was well tolerated. These findings suggest that obicetrapib is an effective therapy for additional lipid lowering in patients with heterozygous familial hypercholesterolemia. ClinicalTrials.gov registration: NCT05425745 .