Phase 2 trial in 102 Japanese patients: obicetrapib 10mg on background statin cuts LDL-C by 45.8% and raises HDL-C by 159% (J Atheroscler Thromb 2024)

Original title: Obicetrapib as an Adjunct to Stable Statin Therapy in Japanese Subjects: Results from a Randomized Phase 2 Trial

J Atheroscler Thromb · 3 April 2024 · 8

Harada-Shiba M, Davdison MH, Ditmarsch M, Hsieh A, Wuerdeman E, Kling D, Nield A, Dicklin MR, Nakata A, Sueyoshi A, Kuroyanagi S, Kastelein JJP

A double-blind, randomised phase 2 trial tested obicetrapib 2.5, 5 or 10 mg daily against placebo for 8 weeks, added to stable statin therapy, in 102 Japanese men and women (mean age 64.8, 71.6% male) who had not reached 2022 Japan Atherosclerosis Society LDL-C or non-HDL-C targets. At the 10 mg dose, obicetrapib significantly lowered median LDL-C by 45.8%, apoB by 29.7% and non-HDL-C by 37.0%, and raised HDL-C by 159% (all P < 0.0001 versus placebo), with similar directional effects at lower doses. The drug was nearly completely eliminated by 4 weeks, was well tolerated, and showed no adverse safety signals, with efficacy and pharmacokinetics comparable to earlier trials in predominantly Caucasian populations. Confirms the lipid effects of obicetrapib extend to an Asian-Pacific population.

Original abstract

Aims: Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor shown to reduce low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), when taken as monotherapy and in combination with ezetimibe on a background of statins, in clinical trials predominantly conducted in Northern European/Caucasian participants. We characterized the efficacy, safety, and tolerability of obicetrapib within an Asian-Pacific region population.

Methods: This double-blind, randomized, phase 2 trial examined obicetrapib 2.5, 5, and 10 mg/d, compared with placebo, for 8 weeks as an adjunct to stable statin therapy (atorvastatin 10 or 20 mg/d or rosuvastatin 5 or 10 mg/d) in Japanese men and women who had not achieved 2022 Japan Atherosclerosis Society Guidelines and had LDL-C ＞70 mg/dL or non-high-density lipoprotein cholesterol (non-HDL-C) ＞100 mg/dL and triglycerides (TG) ＜400 mg/dL. Endpoints included LDL-C, non-HDL-C, HDL-C, very low-density lipoprotein cholesterol, apolipoproteins, TG, steady state pharmacokinetics (PK) in obicetrapib arms, safety, and tolerability.

Results: In the 102 randomized subjects (mean age 64.8 y, 71.6% male), obicetrapib significantly lowered median LDL-C, apoB, and non-HDL-C, and raised HDL-C at all doses; responses in the obicetrapib 10 mg group were -45.8%, -29.7%, -37.0%, and +159%, respectively (all p＜0.0001 vs. placebo). The PK profile demonstrated near complete elimination of drug by 4 weeks. Obicetrapib was well tolerated and there were no adverse safety signals.

Conclusions: All doses of obicetrapib taken as an adjunct to stable statin therapy significantly lowered atherogenic lipoprotein lipid parameters, showed near complete elimination of drug by 4 weeks, and were safe and well tolerated in a Japanese population, similar to previous studies of obicetrapib conducted in predominantly Caucasian participants.

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