Phase 2 trial: obicetrapib plus ezetimibe on top of high-intensity statins cuts LDL-C by 63.4%, with 87% of patients reaching under 55 mg/dL (J Clin Lipidol 2023)

Original title: Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial

J Clin Lipidol · 1 January 2023 · 8

Ballantyne CM, Ditmarsch M, Kastelein JJ, Nelson AJ, Kling D, Hsieh A, Curcio DL, Maki KC, Davidson MH, Nicholls SJ

A double-blind, randomised phase 2 trial gave patients on stable high-intensity statin therapy (LDL-C above 70 mg/dL, triglycerides under 400 mg/dL) obicetrapib 10 mg plus ezetimibe 10 mg (n = 40), obicetrapib 10 mg alone (n = 39), or placebo (n = 40) for 12 weeks. Among ninety-seven patients in the primary analysis (mean age 62.6, 63.9% male, mean BMI 30.9), LDL-C fell by 63.4% with the combination, 43.5% with obicetrapib alone and 6.35% with placebo (P < 0.0001 versus placebo for both active arms). On the combination, 100% of patients reached LDL-C under 100 mg/dL, 93.5% under 70 mg/dL and 87.1% under 55 mg/dL. Both active arms also significantly reduced non-HDL-C, apoB and LDL particle counts. Obicetrapib was well tolerated with no safety issues identified, supporting the combination as a precursor to later phase 3 fixed-dose combination trials.

Original abstract

Background: Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein particles, and apolipoproteins, when added to high-intensity statin in patients with dyslipidemia.

Objective: To evaluate the safety and lipid-altering efficacy of obicetrapib plus ezetimibe combination therapy as an adjunct to high-intensity statin therapy.

Methods: This double-blind, randomized, phase 2 trial administered 10 mg obicetrapib plus 10 mg ezetimibe (n = 40), 10 mg obicetrapib (n = 39), or placebo (n = 40) for 12 weeks to patients with LDL-C >70 mg/dL and triglycerides (TG) <400 mg/dL, on stable high-intensity statin. Endpoints included concentrations of lipids, apolipoproteins, lipoprotein particles, and proprotein convertase subtilisin kexin type 9 (PCSK9), safety, and tolerability.

Results: Ninety-seven patients were included in the primary analysis (mean age 62.6 years, 63.9% male, 84.5% white, average body mass index of 30.9 kg/m2). LDL-C decreased from baseline to week 12 by 63.4%, 43.5%, and 6.35% in combination, monotherapy, and placebo groups, respectively (p<0.0001 vs. placebo). LDL-C levels of <100, <70, and <55 mg/dL were achieved by 100%, 93.5%, and 87.1%, respectively, of patients taking the combination. Both active treatments also significantly reduced concentrations of non-HDL-C, apolipoprotein B, and total and small LDL particles. Obicetrapib was well tolerated and no safety issues were identified.

Conclusion: The combination of obicetrapib plus ezetimibe significantly lowered atherogenic lipid and lipoprotein parameters, and was safe and well tolerated when administered on top of high-intensity statin to patients with elevated LDL-C.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.