P5364Safety profile of bempedoic acid: pooled analysis of 4 phase 3 clinical trials

Abstract

Abstract Background/Introduction Bempedoic acid (BA), an oral, first-in-class, ATP-citrate lyase inhibitor, lowers low-density lipoprotein cholesterol (LDL-C) in patients who do not achieve sufficient lipid lowering with guideline-recommended first-line therapies. Purpose We evaluated the safety profile of BA in phase 3 trials. Methods Data were pooled from 4 randomised, double-blind, placebo-controlled studies that enrolled patients with hyperlipidaemia who were receiving stable lipid-lowering therapy (LLT; maximally tolerated statins +/− nonstatin therapies) and required additional LDL-C lowering. Patients were randomised (2:1) to BA 180 mg or placebo daily for 12 to 52 weeks. Results Median exposure for 3621 patients (2424 BA, 1197 placebo) was 363 days. Background LLT included a statin +/− other LLT (83.8%), nonstatin LLT alone (9.4%), or none (6.8%). Adverse event (AE) and serious AE rates were similar between groups (Table). The most common AEs in the BA and placebo groups were nasopharyngitis (7.4% vs 8.9%), myalgia (4.9% vs 5.3%), and urinary tract infection (4.5% vs 5.5%). Rates of new-onset/worsening diabetes were 4.0% for BA and 5.6% for placebo. No AEs leading to discontinuation differed by ≥0.5% between treatments. All fatal AEs were judged by the investigator as unrelated to treatment. A trend was observed for a lower 3-component major adverse cardiac event rate with BA vs placebo (hazard ratio, 0.85; 95% confidence interval: 0.53 to 1.37). Changes in uric acid, creatinine, and haemoglobin were apparent at week 4, stable over time, and reversible after stopping BA. Gout occurred in 1.4% and 0.4% of patients in the BA and placebo groups, respectively. The safety profile of BA was consistent across background therapies, demographics, and disease characteristics. Table 1. Safety summary Placebo (n=1197) BA (n=2424) Any AE / SAE, % (n) 72.5 (868) / 13.3 (159) 73.1 (1171) / 14.1 (341) Drug discontinuation due to an AE, % (n) 7.8 (93) 11.3 (273) AE with a fatal outcome, % (n) 0.3 (4) 0.8 (19) Aminotransferase elevation >3 x ULN, % (n) 0.3 (3) 0.7 (18) Aminotransferase elevation >5 x ULN, % (n) 0.2 (2) 0.2 (6) Creatine kinase elevation >5 x ULN, % (n) 0.2 (2) 0.3 (8) Creatinine, mean change at week 12, mg/dL −0.002±0.11 0.046±0.12 Uric acid, mean change at week 12, mg/dL −0.02±0.82 0.82±0.97 Haemoglobin, mean change at week 12, g/dL 0.06±0.69 −0.31±0.71 Conclusion(s) BA added to LLT was well tolerated, with a safety profile comparable to placebo.