Bempedoic acid is a convenient, complementary, consistent, once-daily, oral LDL-C lowering drug that significantly reduces elevated LDL-C levels in patients with hypercholesterolemia, including patients inadequately treated with current lipid-modifying therapies. Bempedoic acid, a first-in-class, non-statin, targeted therapy, works in the liver to block cholesterol biosynthesis.
In the liver, bempedoic acid is converted to a coenzyme A (CoA) derivative, or ETC-1002-CoA, which directly inhibits ATP citrate lyase (ACL), a key enzyme that supplies substrate for cholesterol and fatty acid synthesis in the liver. Inhibition of ACL by ETC-1002-CoA results in reduced cholesterol synthesis and upregulation of LDL receptor activity in the liver. This promotes the removal of LDL-C from the blood.
To date, Esperion has completed Phase 2 and Phase 3 clinical studies in over 4,000 patients with over 2,600 patients treated with 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 consistent, complementary LDL-C-lowering efficacy of bempedoic acid and the bempedoic acid / ezetimibe combination pill in patients with atherosclerotic cardiovascular disease (ASCVD), or who are at a high risk for ASCVD, with hypercholesterolemia who continue to have elevated levels of LDL-C despite the use of maximally-tolerated statins and ezetimibe, leaving them at high risk for cardiovascular events. The program includes five studies in approximately 4,000 patients, four for bempedoic acid and one for the bempedoic acid / ezetimibe combination pill.
- Two pivotal studies evaluating bempedoic acid (Studies 1 & 2) in 3,009 patients with ASCVD on maximally-tolerated statin therapy, with top-line results reported in May 2018, and expected in October 2018, respectively;
- Two pivotal studies evaluating bempedoic acid (Studies 3 & 4) in 614 patients with ASCVD, or at a high risk for ASCVD, considered statin intolerant, with top-line results reported in May and March 2018, respectively;
- One pivotal study evaluating the bempedoic acid / ezetimibe combination pill (053 Study) in 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 U.S. Food and Drug Administration (FDA) for bempedoic acid and the bempedoic acid / ezetimibe combination pill 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 second quarter of 2019.
The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined. The company 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) who are only able to tolerate less than the lowest approved daily starting dose of a statin and considered “statin intolerant.” 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.