TA-8995 (obicetrapib) raises ABCA1-specific cholesterol efflux capacity by 28% and preBeta-1 HDL by 36%, showing functional as well as HDL-C gains (J Clin Lipidol 2016)

Original title: Effects of the cholesteryl ester transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density lipoprotein particle subclasses

J Clin Lipidol · 1 January 2016 · 7

van Capelleveen JC, Kastelein JJ, Zwinderman AH, van Deventer SJ, Collins HL, Adelman SJ, Round P, Ford J, Rader DJ, Hovingh GK

A phase 2 trial (NCT01970215) randomised 187 patients with mild dyslipidaemia to placebo, TA-8995 (obicetrapib) 1, 5 or 10 mg, or 10 mg TA-8995 combined with 10 mg rosuvastatin, and measured cholesterol efflux capacity and HDL subclass distribution at baseline and after 12 weeks. Against placebo, 10 mg TA-8995 dose-dependently increased total, non-ABCA1- and ABCA1-specific cholesterol efflux capacity by up to 38%, 72% and 28% respectively, and increased preBeta-1 HDL, the primary acceptor for ABCA1-driven efflux, by 36%. The rise in preBeta-1 HDL correlated significantly with the increase in total and ABCA1-driven efflux capacity, while the HDL-C rise itself did not. The findings indicate TA-8995 improves HDL functional properties beyond simply raising HDL-C levels; whether this translates into cardiovascular benefit required formal testing in an outcomes trial.

Original abstract

Background: TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown.

Objective: To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non-ABCA1-driven CEC and on HDL particle distribution.

Methods: Total, non-ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215).

Results: Compared with placebo, total, non-ABCA1-, and ABCA1-specific CEC were increased dose dependently by up to 38%, 72%, and 28%, respectively, in patients randomized to 10 mg of TA-8995. PreBeta-1 HDL, the primary acceptor for ABCA1-driven cholesterol efflux, was increased by 36%. This increase in preBeta-1 HDL correlated significantly with the total and the ABCA1-driven CEC increase, whereas the high-density lipoprotein cholesterol (HDL-C) increase did not.

Conclusion: TA-8995 dose dependently increased not only total and non-ABCA1-specific CEC but also ABCA1-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor-driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial.

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