Overview of Esperion’s Clinical Studies

Bempedoic Acid Phase 3 Clinical Development

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.

LDL-C Lowering Indication (Total N=3,600)
Study 1; Long-Term, N=2,230
(fully enrolled)
  • 52 wk
Study 2; High Risk, N=779
(fully enrolled)
  • 52 wk
Study 3; SI, N=345
(fully enrolled)
  • 24 wk
Study 4; SI, +EZ, N=269
(fully enrolled)
  • 12 wk

Global regulatory submissions for an LDL-C lowering indication are expected in the first quarter of 2019 for a New Drug Application to the U.S. Food and Drug Administration (FDA) and in the second quarter of 2019 for a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA).

In addition to the bempedoic acid Phase 3 clinical program, Esperion has initiated a global cardiovascular outcomes trial (CVOT), – known as Cholesterol Lowering via BEmpedoic Acid, an ACL-inhibiting Regimen (CLEAR) Outcomes – and expects to submit an NDA to the FDA and an MAA to the EMA for a CVD risk reduction indication, on the basis of a successful completion of the CVOT, in 2022.

CV Risk Reduction Indication
CLEAR Outcomes; (N=~12,600)
  • 4.75 yrs
  • CLEAR Outcomes (1002-043): Cardiovascular event-driven, global, randomized, double-blind, placebo-controlled study expected to enroll approximately 12,600 patients with ASCVD or at high CVD risk and only able to tolerate less than the lowest approved daily starting dose of their statin at more than 1300 sites in approximately 30 countries. The study is expected to enroll over a 30-month period with a total estimated study duration of approximately 4.75 years. Patients enrolling in the study will be required to have baseline LDL-C levels between 100 mg/dL and 190 mg/dL in secondary prevention and >100 mg/dL in primary prevention resulting in an expected mean baseline LDL-C of >135 mg/dL. The primary efficacy endpoint of this event-driven study is the effect of bempedoic acid versus placebo on the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization; also referred to as “four-component MACE”).
  • Study 1 (1002-040; CLEAR Harmony): In May 2018, Esperion announced positive top-line results from the 52-week global, pivotal Phase 3 long-term study (Study 1 or 1002-040) of bempedoic acid 180 mg evaluating the safety and tolerability of bempedoic acid versus placebo in high-risk patients with atherosclerotic cardiovascular disease (ASCVD) who are inadequately controlled with current lipid-modifying therapies, including maximally tolerated statin therapy. Bempedoic acid provided an additional 20 percent LDL-C lowering and a 22 percent hsCRP reduction. In this study, bempedoic acid was observed to be safe and well-tolerated. Final results of Study 1 were presented by Professor Kausik K. Ray, MBChB, MD, MPhil, Professor of Public Health at the School of Public Health, Imperial College London and a Consultant Cardiologist, on August 25 in a Late-Breaking Oral Presentation at the European Society of Cardiology Congress.
    • Additional safety data are being collected in an ongoing open-label extension study (1002-050), and topline results are expected in the fourth quarter of 2019.
  • Study 2 (1002-047; CLEAR Wisdom): Is a 52-week global pivotal Phase 3 randomized, multicenter, double-blind, placebo-controlled study evaluating the safety and efficacy of 180 mg of bempedoic acid versus placebo fully enrolled 779 patients with hypercholesterolemia (with ASCVD and/or HeFH) at high CVD risk and whose LDL-C is not adequately controlled with current lipid-modifying therapies, and who are taking maximally tolerated statin therapy. Top-line results are expected in October 2018.
  • Study 3 (1002-046; CLEAR Serenity): In May 2018, Esperion announced positive top-line results from the 24-week global, pivotal Phase 3 study (Study 3 or 1002-046) of bempedoic acid in patients with ASCVD or at high risk for ASCVD on background therapy of less than approved daily starting doses of statins (high CV risk patients considered statin intolerant). Bempedoic acid provided a 26 percent LDL-C lowering and a 25 percent hsCRP reduction. In this study, bempedoic acid was observed to be safe and well-tolerated.
  • Study 4 (1002-048; CLEAR Tranquility): In March 2018, Esperion announced positive top-line results from the 12-week global, pivotal Phase 3 study (Study 3 or 1002-048) of bempedoic acid 180 mg evaluating the LDL-C lowering efficacy, and safety and tolerability of bempedoic acid versus placebo in patients with ASCVD or at high risk for ASCVD with hypercholesterolemia inadequately treated with background ezetimibe 10 mg and up to the lowest daily starting dose of a statin. Bempedoic acid provided an additional 28 percent LDL-C lowering and a 33 percent hsCRP reduction. In this study, bempedoic acid was observed to be safe and well-tolerated. Final results of Study 4 were presented by Christie M. Ballantyne, M.D., chairman of Esperion’s Phase 3 Executive Committee and Professor and Chief of Cardiology at Baylor College of Medicine in Houston on June 12 in a late breaking oral presentation at the International Symposium on Atherosclerosis. The final results were also simultaneously published as an accepted manuscript in the journal Atherosclerosis.

Bempedoic Acid Phase 2 Recently Completed Studies

In March 2018, Esperion announced positive top-line results from the Phase 2 clinical study (1002-039) that evaluated the LDL-C lowering efficacy, and safety and tolerability of bempedoic acid 180 mg added-on to stable background therapy of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in patients with hypercholesterolemia. Bempedoic acid provided an additional 30 percent LDL-C lowering and a 34 percent hsCRP reduction. In this study, bempedoic acid was observed to be safe and well-tolerated.

In August 2017, Esperion announced positive top-line results from the Phase 2 clinical study (also known as the triplet oral therapy study, 1002-038) which evaluated the LDL-C lowering efficacy, and safety and tolerability of the bempedoic acid / ezetimibe combination (bempedoic acid 180 mg, ezetimibe 10 mg) plus atorvastatin 20 mg, versus placebo, in patients with hypercholesterolemia. The triple combination provided 64 percent LDL-C lowering and a 48 percent hsCRP reduction. In this study, bempedoic acid was observed to be safe and well-tolerated.

For more information, contact Esperion Therapeutics or visit clinicaltrials.gov.