Bempedoic acid is being developed as a once-daily, oral therapy that—in clinical trials to date—has significantly reduced LDL-C levels when added to other lipid-lowering therapies in patients with primary hyperlipidemia who need additional LDL-C lowering. Bempedoic acid is a first-in-class, non-statin, targeted therapy that is designed to primarily work in the liver to inhibit cholesterol biosynthesis.
Bempedoic acid is a prodrug, with an innovative mechanism that is complementary to—yet distinct from—other lipid-lowering therapies, including statins.
Bempedoic acid is converted to its active moiety primarily in the liver, and inhibits adenosine triphosphate citrate lyase (ACL)—an enzyme two steps upstream from HMG-CoA reductase, the target of statins—along the cholesterol biosynthesis pathway. By inhibiting ACL, bempedoic acid reduces cholesterol synthesis, resulting in LDL receptor upregulation and increased clearance of LDL cholesterol from the bloodstream.
Bempedoic acid is converted to its active moiety by ACSVL1, which is not present in skeletal muscle. Therefore, bempedoic acid is not converted to its active moiety within skeletal muscle.
To date, Esperion has completed clinical studies with approximately 3200 patients receiving bempedoic acid.
About Esperion’s Global Pivotal Phase 3 LDL-C Lowering Program
Esperion initiated its global, pivotal, Phase 3 clinical development program in January 2016 to evaluate the safety, tolerability, and LDL-C–lowering efficacy of bempedoic acid and bempedoic acid plus ezetimibe fixed-dose combination. It involves patients with atherosclerotic cardiovascular disease (ASCVD)—or who are at a high risk for ASCVD—and hypercholesterolemia, who continue to have elevated levels of LDL-C despite taking maximally-tolerated statins, leaving them at high risk for cardiovascular events. The program includes 5 studies in approximately 4,000 patients; 4 trials for bempedoic acid and 1 for bempedoic acid plus ezetimibe fixed-dose combination:
- 2 pivotal studies evaluating bempedoic acid: CLEAR Harmony (1002-040) and CLEAR Wisdom (1002-047), comprising 3,009 patients with ASCVD on maximally-tolerated statin therapy, with top-line results reported in May 2018 and October 2018, respectively;
- 2 other pivotal studies evaluating bempedoic acid: CLEAR Serenity (1002-046) and CLEAR Tranquility (1002-048), comprising 614 patients with ASCVD—or at high risk for ASCVD—whose maximally-tolerated statin dose was the lowest approved dose or less, with top-line results reported in May 2018 and March 2018, respectively;
- One pivotal study evaluating bempedoic acid plus ezetimibe fixed-dose combination (1002FDC-053), comprising 382 patients with ASCVD—or at high risk for ASCVD—on maximally-tolerated statin therapy, with top-line results reported in August 2018.
Esperion plans to submit New Drug Applications (NDAs) to the US Food and Drug Administration (FDA)—for bempedoic acid and bempedoic acid plus ezetimibe fixed-dose combination—for LDL–C–lowering indications in the first quarter of 2019. Additionally, Esperion plans to submit Marketing Authorization Applications (MAAs) to the European Medicines Agency (EMA) in the first quarter of 2019.
The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined. Esperion initiated a global cardiovascular outcomes trial (CVOT) to assess the effects of bempedoic acid on the occurrence of major cardiovascular events in patients with—or at high risk for—cardiovascular disease (CVD), and who are only able to tolerate less than the lowest approved daily starting dose of a statin. The CVOT—known as Cholesterol Lowering via Bempedoic Acid, an ACL-inhibiting Regimen (CLEAR) Outcomes—is an event-driven, global, randomized, double-blind, placebo-controlled study, expected to enroll approximately 12,600 patients with hypercholesterolemia and high CVD risk at more than 600 sites in approximately 30 countries.