Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, NEJMoa2415820. https://doi.org/10.1056/NEJMoa2415820 Dr. Stephen J. Nicholls et al.
Points
- The BROADWAY trial evaluated obicetrapib in high-risk cardiovascular patients already on maximum lipid-lowering therapy, comparing its effects to placebo over a 365-day treatment period.
- Obicetrapib significantly reduced LDL cholesterol levels by 29.9 percent compared to a 2.7 percent increase in the placebo group, demonstrating strong lipid-lowering efficacy.
- The treatment also reduced lipoprotein(a) levels by 33.5 percent, an important finding given the limited existing therapies for this cardiovascular risk factor.
- The safety profile of obicetrapib was comparable to placebo, with no significant increase in adverse events reported throughout the study.
- These results support obicetrapib as a promising treatment for patients unable to meet cholesterol targets using current therapies. It offers both LDL and Lp(a) reductions.
Summary
A recent multinational, randomized, placebo-controlled trial, the BROADWAY study, evaluated the efficacy and safety of obicetrapib, a selective cholesteryl ester transfer protein inhibitor, in patients at high risk for cardiovascular events. The study enrolled 2,530 patients with heterozygous familial hypercholesterolemia or a history of atherosclerotic cardiovascular disease, all receiving the maximum tolerated doses of lipid-lowering therapy. Participants were randomly assigned to receive either 10 mg of obicetrapib once daily or a matching placebo for 365 days. The primary endpoint was the percent change in low-density lipoprotein (LDL) cholesterol from baseline to day 84.
The results showed that patients receiving obicetrapib experienced a significant reduction in LDL cholesterol, with a least-squares mean percent change from baseline to day 84 of −29.9% (95% confidence interval [CI], −32.1 to −27.8). In contrast, the placebo group had a modest increase in LDL cholesterol of 2.7% (95% CI, −0.4 to 5.8). The between-group difference was −32.6 percentage points (95% CI, −35.8 to −29.5; P<0.001), highlighting the superior efficacy of obicetrapib in lowering LDL cholesterol. Additionally, a reduction in lipoprotein(a) (Lp(a)) by 33.5% was observed, a significant outcome since Lp(a) is a known risk factor for cardiovascular disease without effective treatments.
The safety profile of obicetrapib was similar to placebo, with no significant differences in adverse events. These findings suggest that obicetrapib offers a promising new treatment option for patients with high cardiovascular risk who struggle to achieve target cholesterol levels with existing therapies. The study demonstrated that obicetrapib lowers LDL cholesterol and reduces Lp(a), presenting a dual benefit for patients with elevated cardiovascular risk.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2415820
References Nicholls, S. J., Nelson, A. J., Ditmarsch, M., Kastelein, J. J. P., Ballantyne, C. M., Ray, K. K., Navar, A. M., Nissen, S. E., Harada-Shiba, M., Curcio, D. L., Neild, A., Kling, D., Hsieh, A., Butters, J., Ference, B. A., Laufs, U., Banach, M., Mehran, R., Catapano, A. L., … Davidson, M. H. (2025). Safety and efficacy of obicetrapib in patients at high cardiovascular risk. New England Journal of Medicine, NEJMoa2415820. https://doi.org/10.1056/NEJMoa2415820
