Long-term Safety and Efficacy of Bempedoic Acid in Japanese Patients with Hypercholesterolemia: the CLEAR-J LONG

Abstract

Aims: Bempedoic acid is an ATP citrate lyase (ACLY) inhibitor acting in the cholesterol biosynthesis pathway. This study evaluated long-term safety and efficacy of bempedoic acid 180 mg/day for 52 weeks in Japanese patients with hypercholesterolemia. Methods: A multicenter, open-label, single-arm Phase 3 long-term study was conducted at 26 hospitals and clinics across Japan in patients aged 18 to 85 years. Newly enrolled patients had previously failed to achieve their lipid management targets because of inadequate response to statins or statin intolerance; rollover patients had completed the 12-week treatment period of a domestic Phase 3 confirmatory study (the CLEAR-J trial) and had not met the discontinuation criteria at Week 12. Results: Bempedoic acid was administered to 130 patients. Treatment-emergent adverse events (TEAEs) occurred in 83.8%, treatment-related TEAEs in 14.6%, serious TEAEs in 6.2%, and AEs leading to discontinuation in 4.6%. None were severe. Between baseline and Week 52, low-density lipoprotein-cholesterol (LDL-C) decreased by 21.6% (overall population) and 25.3% (newly enrolled group), as observed in both statin response subgroups. LDL-C target levels based on risk category were achieved by 65.6% at Week 52 (overall population). Long-term efficacy was also demonstrated for non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Conclusions: Bempedoic acid 180 mg/day for 52 weeks was well tolerated in patients with hypercholesterolemia, with no major safety concerns. Serious AEs were infrequent, and no new safety signals specific to the Japanese population were observed. More than 60% of patients achieved and sustained their LDL-C target levels.