Obicetrapib shows favourable safety in a pooled analysis of phase 3 trials

Obicetrapib, compared with placebo, was associated with a lower risk of adverse events related to diabetes, kidney function decline, and liver function, according to a pooled phase 3 analysis presented by Dr Adam Nelson (Monash University, Australia) [1].

The pooled safety analysis was based on 2 phase 3 trials evaluating obicetrapib 10 mg/day versus placebo: BROOKLYN (NCT05425745) in patients with heterozygous familial hypercholesterolemia, and BROADWAY (NCT05142722) in patients with heterozygous familial hypercholesterolemia or a history of atherosclerotic cardiovascular disease. In both trials, patients had uncontrolled cholesterol levels despite receiving maximally tolerated lipid-lowering therapies. In total, 2,880 participants were included in the pooled analysis, of whom 1,919 patients received obicetrapib and 961 received placebo.

Rates of treatment-emergent adverse events, discontinuations due to adverse events (AEs), and serious AEs were similar between the obicetrapib and placebo groups. An analysis of AEs of special interest showed a reduced risk with obicetrapib versus placebo for new-onset diabetes mellitus or worsening glycaemic control (32.9% vs 37.6%; RR 0.88; 95% CI 0.79–0.97), decline in eGFR (6.7% vs 8.7%; RR 0.77; 95% CI 0.59–1.00), increases in bilirubin to >2 times upper limit of normal (0.1% vs 0.7%; RR 0.17; 95% CI 0.03–0.83), and increases in serum creatinine of ≥0.3 mg/dL (5.0% vs 7.3%; RR 0.69; 95% CI 0.51–0.93).

In contrast, rates of increase in transaminases and creatine kinase, as well as events indicative of heart failure and changes in heart rhythm and blood pressure, were similar between treatment groups.

Overall, the safety profile in this pooled analysis was consistent with that reported in the individual trials. Dr Nelson concluded that “this analysis supports the safety and tolerability of obicetrapib in patients with high cardiovascular risk. If confirmed in larger and adequately powered trials, the safety profile of obicetrapib with respect to hepatic, renal, muscle, and glycaemic events may favourably differentiate it from other available lipid-lowering therapies.”

Nelson AJ, et al. Safety of obicetrapib: An integrated pooled phase III safety analysis. ACC, 28–30 March 2026, New Orleans, LA, USA.