Obicetrapib Lowers LDL-C in Patients Taking High Intensity Statins - Results from the ROSE Clinical Trial

Abstract

Lead Author's Financial Disclosures New Amsterdam Pharma. Study Funding NewAmsterdam Pharma. Background/Synopsis Mendelian randomization studies have predicted that cholesteryl ester transfer protein (CETP) inhibition would reduce the risk of cardiovascular events. This was confirmed in REVEAL; by lowering LDL-C, anacetrapib was associated with a reduction in cardiovascular events. Early studies of the selective CETP inhibitor obicetrapib demonstrated LDL-C lowering up to 45% as monotherapy and 68% in combination with moderate intensity statin therapy. Objective/Purpose To assess the effects of obicetrapib on LDL-C and lipid parameters in patients treated with high intensity statins. Methods Patients (n=120) with an LDL-C ≥70 mg/dL, despite treatment with high intensity statins, were randomized to treatment with obicetrapib 5 or 10 mg or matching placebo for 8 weeks. The primary endpoint was the difference between groups in percent change in LDL-C from baseline to week 8. Secondary endpoints included changes in ApoB, non-HDL-C and HDL-C. Exploratory analyses evaluated differences in Friedewald and preparative ultracentrifugation measurement (PUC) of LDL-C. Safety assessment included biochemistry, vital signs, physical examinations, and adverse events. Results Patients had a median LDL-C of 88 mg/dL at baseline. Compared with placebo, obicetrapib produced greater dose-dependent lowering of LDL-C (up to 50.8%, P<0.0001), which was comparable between PUC and Friedewald measures. Obicetrapib also produced greater lowering of apoB (up to 29.8%, P<0.0001), non-HDL-C (up to 44.4%, P<0.0001), Lp(a) (up to 56.5%, P<0.0001) and raising of HDL-C (up to 165%, P<0.0001) in a dose-dependent fashion compared with placebo. Fewer patients in the obicetrapib arms (26%) experienced treatment-emergent adverse events than in the placebo arm (48%). No patients in either obicetrapib arm experienced a treatment-emergent SAE. There were no clinically significant changes in laboratory parameters, vital signs, or physical examinations in any study group. Conclusions Obicetrapib at doses of 5 and 10 mg produced robust decreases in LDL-C, ApoB, Lp(a) and Non-HDL-C and increases in HDL-C compared to placebo in patients treated with high intensity statins and was safe and well tolerated. New Amsterdam Pharma.