Efficacy and Safety of Bempedoic Acid for Hypercholesterolemia in Japan: A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Finding Trial

Aim: We evaluated the efficacy and safety of bempedoic acid, an ATP-citrate lyase inhibitor, at doses of 60, 120, and 180 mg, administered for 12 weeks in conjunction with ongoing treatments (e.g., statin and/or other lipidmodifying therapy) and determined the phase 3 trial dosage in Japanese patients. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial included patients with hypercholesterolemia at risk for cardiovascular events and an inadequate response to statins/statin intolerance. The percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 was calculated. Results: The bempedoic acid 60 mg, 120 mg, 180 mg, and placebo groups included 47, 46, 48, and 47 patients, respectively; 79% of patients had an inadequate response to statins and 21% had statin intolerance. Relative to placebo (-1.9%), LDL-C reduction from baseline to week 12 was significantly greater in the bempedoic acid treatment groups (least squares mean: 60 mg, -10.6%; 120 mg, -21.9%; 180 mg, -21.3%; p<0.01 vs. placebo). Patients with an inadequate response and statin intolerance who were treated with bempedoic acid showed improved LDL-C levels by week 12. The incidence of treatment-emergent adverse events was higher in the bempedoic acid-treated groups (60 mg, 57.4%; 120 mg, 54.3%; and 180 mg, 58.3%) than in the placebo group (38.3%). There was no increasing trend with increasing doses. Adverse events related to muscular and hepatic disorders were infrequent, and no new or worsening cases of diabetes were reported. Conclusions: The efficacy and safety of bempedoic acid in Japanese patients with elevated LDL-C levels were confirmed. The 180 mg dosage of bempedoic acid was found to be appropriate for a Japanese phase 3 trial.