A new clinical trial found that once-daily obicetrapib, an investigational cholesteryl ester transfer protein inhibitor, lowered low-density lipoprotein cholesterol by 29.9% in patients at high cardiovascular risk who were already receiving maximum tolerated lipid-lowering therapy.
The randomized, placebo-controlled trial enrolled 2,530 adult patients with either atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia. All participants were receiving statins at the highest tolerated dose, with or without ezetimibe, bempedoic acid, or PCSK9 inhibitors. Despite this background therapy, many patients remained above recommended lipid targets.
Participants were randomly assigned in a 2:1 ratio to receive either 10 mg of obicetrapib or placebo once daily for 12 months. The mean age was 65 years, and 34% of participants were female. At baseline, mean low-density lipoprotein (LDL) cholesterol was 98 mg/dL.
At day 84, patients in the obicetrapib group had a 29.9% reduction in LDL cholesterol, compared with a 2.7% increase in the placebo group, for a between-group difference of −32.6 percentage points. At that time point, 51.0% of patients in the obicetrapib group had achieved LDL cholesterol levels less than 55 mg/dL, and 27.9% dropped below 40 mg/dL. These levels are consistent with guideline-based targets for high-risk individuals.
Other lipid measures also improved with obicetrapib. Non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and triglycerides declined to a greater extent than with placebo. HDL cholesterol and apolipoprotein A1 levels increased significantly in the obicetrapib group.
The LDL-lowering effect persisted over 12 months, though it diminished slightly by day 365. At study end, the obicetrapib group had a 25.3% reduction in LDL cholesterol compared with a 1.3% decrease with placebo.
Adverse events occurred in 59.7% of obicetrapib-treated patients and 60.8% of those receiving placebo. Serious adverse events were reported in 12.5% and 13.9% of the two groups, respectively. No significant between-group differences were observed in the incidence of new-onset diabetes, worsening glycemic control, or impaired kidney function. Cardiovascular events occurred in 4.2% of patients receiving obicetrapib and 5.2% of those receiving placebo. However, the trial was not powered to assess clinical outcomes.
No major safety signals were identified during the study. These findings suggest that obicetrapib may offer an effective oral option to further reduce LDL cholesterol in patients already receiving intensive lipid-lowering therapy.
A long-term outcomes trial is ongoing to evaluate whether obicetrapib reduces cardiovascular event rates (ClinicalTrials.gov identifier: NCT05202509).
Disclosures are available in the published article.