Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial
File(s)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2026-03-01
Date Acceptance
2025-12-11
Citation
Nature Medicine, 2026, 32 (3), pp.1052-1060
ISSN
1078-8956
Publisher
Nature Research
Start Page
1052
End Page
1060
Journal / Book Title
Nature Medicine
Volume
32
Issue
3
Copyright Statement
Copyright © 2026 Springer Nature. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41760952
PII: 10.1038/s41591-025-04179-4
Subjects
Humans
Hyperlipoproteinemia Type II
Female
Male
Cholesterol, LDL
Middle Aged
Adult
Anticholesteremic Agents
Cholesterol Ester Transfer Proteins
Heterozygote
Apolipoproteins B
Double-Blind Method
Benzimidazoles
Treatment Outcome
Aged
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2026-02-27