For patients with heterozygous familial hypercholesterolemia (HeFH), achieving adequate low-density lipoprotein cholesterol (LDL-C) lowering remains a significant challenge. New results from the BROOKLYN trial suggest that the investigational agent obicetrapib could be an effective add-on therapy for this high-risk population.¹
Mechanism of Action
Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor. By inhibiting CETP, it prevents the transfer of cholesteryl esters from high-density lipoproteins (HDL) to apolipoprotein B-containing lipoproteins, which is intended to lower LDL-C and increase HDL-C levels.
Methodology
The BROOKLYN trial (NCT05425745) was a randomised, placebo-controlled study designed to evaluate the efficacy and safety of obicetrapib.¹ The trial enrolled 354 patients with HeFH who had an LDL-C level of ≥70 mg/dL while on maximally tolerated lipid-lowering therapy. Participants were randomised in a 2:1 ratio to receive either obicetrapib 10 mg or a placebo, taken daily for 365 days. The primary endpoint was the percentage change in LDL-C from baseline to day 84.
Results
The study met its primary endpoint. At day 84, treatment with obicetrapib resulted in a placebo-adjusted mean reduction in LDL-C of 36.3% (95% CI -42.2% to -30.4%; P < 0.0001).¹
Significant improvements were also observed in key secondary endpoints at day 84. Obicetrapib led to placebo-adjusted reductions in apolipoprotein B by 24.4%, non-HDL cholesterol by 34.5%, and lipoprotein(a) by 45.9%. Furthermore, a substantial placebo-adjusted increase in HDL cholesterol of 138.7% was reported. The treatment was well tolerated by patients throughout the study.
Interpretation
These findings indicate that obicetrapib provides significant additional lipid lowering for patients with HeFH who are unable to reach their treatment goals with current standard-of-care therapies. The reduction in multiple atherogenic lipoproteins, including LDL-C and lipoprotein(a), suggests a potential new therapeutic option to help manage cardiovascular risk in this patient group.
Next Steps
The long-term cardiovascular outcomes of obicetrapib are being evaluated in the ongoing BROADWAY trial.²
This study was funded by NewAmsterdam Pharma.
Disclaimer
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References
1. Nicholls SJ, Nelson AJ, Ditmarsch M, et al. Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial. Nat Med (2026). https://doi.org/10.1038/s41591-025-04179-4
2. Nicholls SJ, Ditmarsch M, Kastelein JJP, et al. Obicetrapib on top of maximally tolerated lipid-modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN. Am Heart J. 2024;274:32-45. https://doi.org/10.1016/j.ahj.2024.05.002