Obicetrapib lowers LDL-c in patients with HeFH

In the BROOKLYN trail, obicetrapib lowered LDL-c at day 84 and 365 compared with placebo in patients with HeFH and LDL-c ≥70 mg/dL despite maximally tolerated lipid-lowering therapy.

This summary is based on the publication of Nicholls SJ, Nelson AJ, Ditmarsch M, et al. - Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial. Nat Med. 2026 Feb 27. [Online ahead of print] doi: 10. 1038/s41591-025-04179-4.

Introduction and methods

Background

Patients with HeFH often fail to reach recommended LDL-c targets and remain at high risk of cardiovascular disease [1-2]. Lipid-lowering therapies beyond statins are infrequently used in this patient population [2-3]. Obicetrapib is a selective oral cholesteryl ester transfer protein (CETP) inhibitor that lowers LDL-c and raises HDL-c [4-8].

Aim of the study

The aim of the study was to evaluate the efficacy and safety of obicetrapib in patients with HeFH and LDL-c ≥70 mg/dL despite maximally tolerated lipid-lowering therapy.

Methods

The BROOKLYN (Evaluate the Effect of Obicetrapib in Patients with HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies) trial was a randomized, placebo-controlled trial in which 354 adults with HeFH and who were treated with maximally tolerated lipid-lowering therapy were randomized in a 2:1 ratio to receive obicetrapib 10 mg daily (n=236) or placebo (n=118) for 365 days. Key inclusion criteria were LDL-c ≥70 mg/dL, triglycerides <400 mg/dL and an eGFR ≥30 mL/min/1.73 m².

Participants had a mean baseline LDL-c level of 122 mg/dL and most were receiving statin therapy (87%). Ezetimibe was used in 53% of participants and PCSK9 inhibitors in 16% of participants.

Outcomes

The primary endpoint was the percent change in LDL-c from baseline to day 84.

Main results

Efficacy

• At day 84, the mean percentage change in LDL-c was −36.1% in the obicetrapib group and 0.3% in the placebo group (placebo-adjusted change: −36.3%; 95%CI: −42.2 to −30.4; P<0.0001).
• More patients treated with obicetrapib achieved key LDL-c thresholds at day 84 compared with placebo:
  •  LDL-c <40 mg/dL: 16.3% vs. 0.9%
  • LDL-c <55 mg/dL: 31.3% vs. 2.6% 
  • LDL-c <70 mg/dL: 51.1% vs. 11.4%
  • LDL-c <100 mg/dL: 77.1% vs. 39.5%
• At day 365, the placebo-adjusted LDL-c change with obicetrapib was −41.5% (95%CI: −51.5 to −31.8; P<0.001).
• At day 84, treatment with obicetrapib resulted in placebo-adjusted changes in apoB of −24.4% (95%CI: −28.6 to −20.2), in non HDL-c of −34.5% (95%CI: −39.7 to −29.2), in triglycerides of −11.7% (95%CI: −21.5 to −2.0), in Lp(a) of −45.9% (95%CI: −65.9 to −26.0) and HDL-c of +138.7% (95%CI: 126.4 to 150.9).

Safety

• The incidence of treatment-emergent adverse events was similar between the groups (63.7% in the obicetrapib group vs. 70.3% in the placebo group).
• There were also no differences in the incidences of serious adverse events (5.6% vs. 6.8%), study drug-related treatment-emergent adverse events (4.3% vs. 6.8%) or treatment-emergent adverse events leading to withdrawal from treatment (4.3% vs. 6.8%) between the obicetrapib and placebo groups.

Conclusion

In the BROOKLYN trial among patients with HeFH on maximally tolerated lipid-lowering therapy, treatment with obicetrapib resulted in significantly lower LDL-c levels at day 84 and 365 compared with placebo. Obicetrapib also reduced apoB, non-HDL-c and Lp(a) compared with placebo. Obicetrapib appeared to be well tolerated.

Find this article online at Nat Med.

References

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