Overview of Esperion’s Clinical Studies

Bempedoic Acid Recently Completed Studies

Esperion announced in August 2017 top-line results from 1002-038, a Phase 2 clinical study, also known as the triplet oral therapy study, evaluating the LDL-C lowering efficacy and safety of the bempedoic acid / ezetimibe combination (bempedoic acid 180 mg, ezetimibe 10 mg) plus atorvastatin 20 mg, versus placebo, in patients with hypercholesterolemia. The six-week study met its primary endpoint of greater LDL-C lowering from baseline of 64 percent (p<0.001) in the bempedoic acid / ezetimibe combination with atorvastatin group, as compared to placebo. Ninety five percent of patients receiving treatment achieved greater than or equal to 50 percent LDL-C lowering reduction and 90 percent achieved LDL-C levels of less than 70 mg/dL. The bempedoic acid / ezetimibe combination with atorvastatin also demonstrated a reduction of 48 percent (p<0.001) in high-sensitivity C-reactive protein (hsCRP), an important marker of the underlying inflammation associated with cardiovascular disease. The bempedoic acid / ezetimibe combination with atorvastatin was observed to be safe and well-tolerated.

Esperion has studied bempedoic acid in approximately 1,300 patients and treated over 800 patients across multiple Phase 1 and Phase 2 studies. Learn more about previously completed clinical studies.

Bempedoic Acid Recently Initiated Studies (Phase 3)

The global Phase 3 clinical development program initiated in January 2016 with the start of a long-term safety study, Study 1. The Company initiated in December 2016 three remaining global pivotal Phase 3 LDL-C lowering efficacy studies. The overall Phase 3 program – including the ongoing long-term safety study and three LDL-C lowering efficacy studies in high cardiovascular disease (CVD) risk patients; those with atherosclerotic cardiovascular disease (ASCVD), heterozygous familial hypercholesterolemia (HeFH) and patients considered statin intolerant – is fully enrolled with over 3,600 high CVD risk patients with hypercholesterolemia on optimized background lipid-modifying therapy, specifically patients with ASCVD and/or HeFH who have LDL-C levels of ≥100 mg/dL; and patients who are only able to tolerate less than the lowest approved daily starting dose of their statin (statin intolerant).

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

Top-line results from the four global pivotal Phase 3 studies are expected by the second and third quarters of 2018. Global regulatory submissions for an LDL-C lowering indication are expected by the first quarter of 2019 for a New Drug Application to the U.S. Food and Drug Administration (FDA) and 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 a NDA to the FDA for a CVD risk reduction indication, on the basis of a successful completion of the CVOT, by 2022.

CV Risk Reduction Indication
CLEAR Outcomes; (N=~12,600)
  • 4.75 yrs
  • CLEAR Outcomes: Event-driven, global, randomized, double-blind, placebo-controlled study expected to enroll approximately 12,600 patients with hypercholesterolemia or at high CVD risk and only able to tolerate less than the lowest approved daily starting dose of their statin at more than 600 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 of >135 mg/dL. The primary efficacy endpoint of the 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”).
  • Global Pivotal Phase 3 Study 1: 52-week global pivotal Phase 3 randomized, double-blind, placebo-controlled study evaluating the long-term safety and tolerability of 180 mg of bempedoic acid versus placebo fully enrolled 2,230 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 by the second quarter of 2018.
    Additional safety data will be collected in an open-label extension study beyond the specific duration of conduct for Study 1.
  • Global Pivotal Phase 3 Study 2: 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 by the third quarter of 2018.
  • Global Pivotal Phase 3 Study 3: 24-week global pivotal Phase 3 randomized, multicenter, double-blind, placebo-controlled study evaluating the LDL-C lowering efficacy of 180 mg of bempedoic acid versus placebo fully enrolled 345 high CVD risk patients with hypercholesterolemia (with ASCVD and/or HeFH), or who are high risk primary prevention, whose LDL-C is not adequately controlled with current lipid-modifying therapies, and who are only able to tolerate less than the lowest approved daily starting dose of a statin and considered statin intolerant. Top-line results are expected by the second quarter of 2018.
  • Global Pivotal Phase 3 Study 4: 12-week global pivotal Phase 3 randomized, multicenter, double-blind, placebo-controlled study evaluating the efficacy of 180 mg of bempedoic acid versus placebo as an add-on to 10 mg of ezetimibe fully enrolled 269 high CVD risk patients with hypercholesterolemia (with ASCVD and/or HeFH), whose LDL-C is not adequately controlled with current lipid-modifying therapy, including ezetimibe, and who are only able to tolerate less than the lowest approved daily starting dose of a statin and considered statin intolerant. Top-line results are expected by the second quarter of 2018.

Bempedoic Acid Recently Initiated Studies (Phase 2)

Esperion initiated in July 2017 a Phase 2 clinical study (1002-039) to assess the efficacy and safety of bempedoic acid when added-on to an injectable proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) therapy. This non-registrational study will assess the incremental LDL-C lowering efficacy and continued safety and tolerability of a once-daily, oral bempedoic acid pill added-on to an injectable biologic therapy in patients with elevated LDL-C levels. The study is expected to enroll approximately 50 patients with hypercholesterolemia at approximately 20 sites across the U.S.  Top-line results are expected by the first quarter of 2018.

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