ROSE2: Obicetrapib/ezetimibe combination further lowers LDL in statin-treated patients
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Key takeaways:
- A combination of obicetrapib and ezetimibe further lowered LDL in statin-treated patients with dyslipidemia.
- A fixed-dose combination pill of obicetrapib and ezetimibe will be developed.
In statin-treated patients with dyslipidemia, the combination of obicetrapib and ezetimibe further lowered LDL, according to the results of the phase 2 ROSE2 trial.
As Healio previously reported, obicetrapib (NewAmsterdam Pharma), an investigational cholesteryl ester transfer protein (CETP) inhibitor, decreased LDL, non-HDL, lipoprotein(a) and apolipoprotein B and increased HDL at 8 weeks in the ROSE trial of patients with dyslipidemia on statin therapy.
Data were derived from Davidson MH, et al. Late Breakers. Presented at: National Lipid Association Scientific Sessions; June 1-4, 2023; Atlanta (hybrid meeting).
For the ROSE2 trial, presented at the National Lipid Association Scientific Sessions and published in the Journal of Clinical Lipidology, the researchers randomly assigned 119 patients with LDL greater than 70 mg/dL and triglycerides less than 400 mg/dL on a stable dose of a high-intensity statin to obicetrapib 10 mg daily plus ezetimibe 10 mg daily, obicetrapib 10 mg daily alone or placebo.
“The cardiovascular event rates are climbing and the amount of patients not adequately treated is also extremely high,” Healio | Cardiology Today Editorial Board Member Michael H. Davidson, MD, FACC, FACP, FNLA, CEO of NewAmsterdam Pharma and clinical professor of medicine and director of the Lipid Clinic at University of Chicago Medicine, said during a presentation. “New guidelines and expert reports recommend target LDLs of less than 55 mg/dL for very high-risk patients. Therefore ... a lot more patients need more aggressive approaches to managing atherosclerotic cardiovascular disease with lower LDL cholesterol levels.”
The primary outcome of change in LDL between baseline and 12 weeks was assessed in an on-treatment analysis of 97 patients (mean age, 63 years; 64% men; 85% white; mean BMI, 30.9 kg/m2).
The median percentage change in LDL between baseline and 12 weeks was –6.4% in the placebo group, –43.5% in the obicetrapib-only group and –63.4% in the obicetrapib/ezetimibe group (P vs. placebo for both obicetrapib groups < .0001), according to the researchers.
The LDL target of less than 55 mg/dL was attained by no one in the placebo group, 42.3% of the obicetrapib-only group and 87.1% of the obicetrapib/ezetimibe group, Davidson said during the presentation, noting that the target of less than 70 mg/dL was attained by 16.7% of the placebo group, 73.1% of the obicetrapib-only group and 93.5% of the obicetrapib/ezetimibe group, and the target of less than 100 mg/dL was attained by 66.7% of the placebo group, 88.5% of the obicetrapib-only group and 100% of the obicetrapib/ezetimibe group.
HDL increased in the obicetrapib-only group by 142% and in the obicetrapib/ezetimibe group by 136% (P vs. placebo for both < .0001), the researchers found.
Total LDL particles decreased by –5.7% in the placebo group, –54.8% in the obicetrapib-only group and –72.1% in the obicetrapib/ezetimibe group (P vs. placebo for both < .0001), and small LDL particles decreased more in the obicetrapib groups than the placebo group (P vs. placebo for both < .0001), Davidson said, adding that LDL particle size increased in the obicetrapib groups and decreased in the placebo group (P vs. placebo for both < .0001). He said all three metrics were optimal in the obicetrapib groups but not in the placebo group.
There was no difference in drug discontinuation rates between the groups, and there were fewer adverse events in the obicetrapib groups than in the placebo group, Davidson said.
The effect on LDL of adding ezetimibe to obicetrapib was greater than the effect of adding ezetimibe to statin therapy, which may have to do with “enhanced intestinal clearance” of LDL, he said.
“With this data, we are moving forward with a fixed-dose combination tablet ... and we will initiate phase 3 in early 2024,” Davidson said.
Reference:
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Davidson MH, et al. Late Breakers. Presented at: National Lipid Association Scientific Sessions; June 1-4, 2023; Atlanta (hybrid meeting).
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