Nonstatin therapy obicetrapib promising for addressing unmet medical needs for high CV risk patients
Netherlands: CETP inhibitor drug obicetrapib has the potential to address the unmet medical need for patients at high cardiovascular risk, a recent study has concluded.
The study, published in the journal Nature Medicine, showed the effectiveness of obicetrapib 5 mg and 10 mg as an additional treatment to high-intensity statins for a robust reduction in LDL-C, Apo B, non-HDL-C, and Lp(a) and increasing HDL-C and Apo A1 in comparison to placebo. This refutes the therapy that such cholesteryl ester transfer protein (CETP) inhibitor-driven effects would be diminished when used in addition to high-intensity statins.
Current guidelines for managing high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Nonstatin options have limitations and statin therapy alone is not sufficient to reach goals. Stephen J. Nicholls, Victorian Heart Institute, Monash University, Clayton, Victoria, Australia, and colleagues tested the lipid-lowering effects of the CETP inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial. The trial was conducted in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl−1) with background high-intensity statin treatment.
The study revealed the following findings:
- Treatment with 5 mg or 10 mg obicetrapib over the course of 8 weeks resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%), the primary trial outcome.
- As compared with placebo, obicetrapib treatment also significantly decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile.
"The trial expanded the growing body of evidence to support the tolerability and safety of this specific CETP inhibitor," the researchers wrote. "Considering the unmet medical need for additional therapies for a substantial reduction in LDL-C in patients at high cardiovascular risk, the results from ROSE are promising."
"Additional phase 3 investigations including a cardiovascular outcomes trial are currently underway for further assessment of the safety and clinical benefits of obicetrapib," they concluded.
Reference:
Nicholls, S.J., Ditmarsch, M., Kastelein, J.J. et al. Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial. Nat Med 28, 1672–1678 (2022). https://doi.org/10.1038/s41591-022-01936-7
