Safety and efficacy of obicetrapib in patients at high cardiovascular risk
File(s)
Accepted version
Author(s)
Type
Journal Article
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 lipidlowering 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.)
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 lipidlowering 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.)
Date Issued
2025-07-03
Date Acceptance
2025-05-01
Citation
New England Journal of Medicine, 2025, 393 (1), pp.51-61
ISSN
0028-4793
Publisher
Massachusetts Medical Society
Start Page
51
End Page
61
Journal / Book Title
New England Journal of Medicine
Volume
393
Issue
1
Copyright Statement
Copyright © 2025 Massachusetts Medical Society. 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/40337982
Subjects
CHOLESTEROL
General & Internal Medicine
Life Sciences & Biomedicine
Medicine, General & Internal
Science & Technology
TA-8995
THERAPY
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-05-07