Obicetrapib Works Synergistically with Ezetimibe in Statin Users, Study Finds

New data indicates obicetrapib monotherapy could provide a synergistic benefit on lipid particles when used in combination with ezetimibe in people already on high-intensity statin therapy.¹

The presentation, which was delivered at the American College of Cardiology 2024 (ACC.24) Annual Scientific Session, comes just 2 days prior to New Amsterdam’s announcing their phase 3 outcomes trial of the agent, named PREVAIL, had met its target enrollment of more than 9000 patients.^1,2

“Cardiovascular disease is one of the most common causes of death and disability globally,” said Stephen Nicholls, MBBS, PhD, director of the Monash Victorian Heart Institute, professor of cardiology at Monash University, and primary investigator on the Phase 3 PREVAIL trial.² “Despite widespread availability of statin therapies, CVD-related deaths are on the rise, and many patients are not at their risk-based LDL-C goals. Based on clinical data to-date, we believe obicetrapib can meaningfully improve a range of lipid and lipoprotein measurements associated with CVD risk, which could translate into improved long-term outcomes for those patients."

A novel, oral, low-dose CETP inhibitor, obicetrapib has been the subject of multiple phase 2 trials conducted by NewAmsterdam, including TULIP, ROSE, OCEAN, and ROSE2. The ACC.24 presentation was an analysis of data from the ROSE2 trial, which was initially presented at the National Lipid Association Scientific Sessions in June 2023.^1,2,3

In the trial, patients with LDL-C greater than 70 mg/dL while taking high-intensity statin therapy were randomized in a 1:1:1 ratio to obicetrapib plus ezetimibe, obicetrapib 10 mg, or placebo for 12 weeks. The primary outcome of the trial was the percent change from baseline to week 12 in Friedewald-calculated LDL-C for the obicetrapib plus ezetimibe combination treatment group compared with placebo. Secondary outcomes of interest included percent changes from baseline to week 12 in LDL-C for obicetrapib monotherapy compared with placebo and in ApoB for the obicetrapib plus ezetimibe combination compared with placebo and the obicetrapib monotherapy compared with placebo.³

Results of the trial pointed to LDL-C reductions of 63.4%, 43.5%, and 6.35% in combination, monotherapy, and placebo groups, respectively, at 12 weeks (P < .0001). Further analysis suggested LDL-C target goals of less than 100 mg/dL, less than 70 mg/dL, and less than 55 mg/dL at week 12 were achieved by 100%, 93.5%, and 87.1%, respectively, of patients taking the combination obicetrapib with ezetimibe.³

At ACC.24, Michael H. Davidson, MD, professor of Medicine and Director of the Lipid Clinic at the University of Chicago as well as the chief executive officer of NewAmsterdam, presented data detailing the synergistic effects of obicetrapib and ezetimibe on circulating LDL particles from within the ROSE2 trial. The primary outcomes of interest for this analysis were changes in LDL-C, and non-HDL-C, lipoprotein particles (-P), Apo B, sdLDL-C, other lipid biomarkers and safety.

Upon analysis, results demonstrated obicetrapib use, as a monotherapy and in combination with ezetimibe, significantly (all P < .05) reduced LDL-C (43.5 and 63.4%), non-HDL-C (37.5 and 55.6%), ApoB (24.2 and 34.4%), total LDL- P (54.8 and 72.1%), small LDL-P (92.7 and 95.4%), and sdLDL-C (30.9 and 44.4%), and increased HDL-C (142% and 136%) at 12 weeks.

For more insight into this study, obicetrapib, and how this new data further informs the understanding of its safety and efficacy profile, check out our full ACC.24 interview with study investigator Christie Ballantyne, MD, chief of Cardiovascular Research and professor at Baylor College of Medicine

Relevant disclosures for Ballantyne include Arrowhead, AstraZeneca, Eli Lilly and Company, Abbott Diagnostics, NewAmsterdam, and others.

References:

1. Hsieh A, Davidson MH, Ditmarsch M, et al. SYNERGISTIC EFFECT OF OBICETRAPIB AND EZETIMIBE ON CIRCULATING LDL PARTICLES. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
2. Ballantyne CM, Ditmarsch M, Kastelein JJ, et al. Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial. J Clin Lipidol. 2023;17(4):491-503. doi:10.1016/j.jacl.2023.05.098