Obicetrapib safety analysis: Pooled phase 3 clinical trial experience.

Background: Obicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that lowers LDL-C and raises HDL-C. Although prior studies have demonstrated efficacy and general tolerability, a comprehensive evaluation of its safety profile across later-stage clinical trials is needed. Methods: Safety outcomes were assessed in a pooled analysis of two phase III trials comparing obicetrapib 10 mg daily with placebo in adults with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD). Participants received treatment for 365 days. Safety endpoints included treatment-emergent adverse events (TEAEs) and prespecified events of special interest including hepatic, muscular, glycemic, renal and ocular parameters as well as overall rates of discontinuation. Results: A total of 2,880 participants were included (mean age 64 years; 36 % female; 82 % with ASCVD; 35.8 % with diabetes). Overall TEAE rates were similar between obicetrapib and placebo (60.2 % vs 62.0 %). AEs leading to treatment discontinuation occurred in 4.1 % of obicetrapib-treated participants and 5.3 % on placebo, Risk Ratio (RR) 0.77 [0.54-1.08]. No clinically significant change in blood pressure was observed between groups and hypertension events were comparable. There was no difference between the groups in liver or muscle-related endpoints. Reduction in eGFR occurred less often with obicetrapib ( compared to placebo (6.7 % vs. 8.7 % RR 0.77 [0.59, 1.00])). Macular degeneration was reported once in the obicetrapib group (n= 1 [0.1 %]). Deaths were similar between treatment groups. No new safety signals were identified. Conclusions: Obicetrapib demonstrated a favorable safety profile over 12 months, with AE rates comparable to placebo. These findings extend our understanding of the safety and tolerability of obicetrapib.