Overview of Esperion’s Clinical Studies

Bempedoic Acid Recently Completed Studies

Esperion announced in October 2016 top-line results from 1002-035, a Phase 2 pharmacokinetics and pharmacodynamics (PK/PD) study of bempedoic acid added to atorvastatin 80, which demonstrated the eight-week study met its primary endpoint of greater LDL-C lowering from baseline of 22 percent (p=0.0028) with bempedoic acid 180 mg compared with placebo with all patients on a background of atorvastatin 80 mg. Bempedoic acid also demonstrated an incremental reduction of 35 percent (p=0.0020) in high-sensitivity C-reactive protein (hsCRP), an important marker of the underlying inflammation associated with cardiovascular disease. Bempedoic acid added to atorvastatin 80 mg produced no clinically relevant effects on atorvastatin PK, and appeared to be safe and well-tolerated, with no serious adverse events reported.

Based on positive top-line results from the 1002-035 as described above, and the previously completed Phase 1 and Phase 2 studies, the global pivotal Phase 3 program will include patients with hypercholesterolemia on any statin at any dose.

Esperion has studied bempedoic acid in eighteen completed clinical studies, including ten Phase 1 studies, and eight Phase 2 studies. Learn more about previously completed clinical studies.

Bempedoic Acid Recently Initiated Studies

The global Phase 3 clinical development program initiated in January 2016 with the start of a long-term safety study, Study 1. The Company recently announced the initiation of three remaining global pivotal Phase 3 LDL-C lowering efficacy studies. The overall Phase 3 program – including the ongoing long-term safety study and the 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 designed to enroll over 3,200 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=~3400)
Study 1; Long-Term, N=2230
(fully enrolled)
  • 52 wk
Study 2; High Risk, N=750
(fully enrolled)
  • 52 wk
Study 3; SI, N=300
(fully enrolled)
  • 24 wk
Study 4; SI, +EZ, N=225
  • 12 wk

Top-line results from the global Phase 3 program in its entirety are expected by mid-2018. Global regulatory submissions for an LDL-C lowering indication are expected in the first half 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 Phase 3 clinical program, Esperion has also 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)
  • 5 yrs
  • CLEAR Outcomes: Event-driven, global, randomized, double-blind, placebo-controlled study expected to enroll approximately 12,600 patients with hypercholesterolemia and high CVD risk who are considered to be statin intolerant 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 greater than or equal to 100 mg/dL in primary prevention. Expected mean baseline will be 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 (2233 ASCVD and/or HeFH patients): 52-week global pivotal Phase 3 randomized, double-blind, placebo-controlled study evaluating the long-term safety of 180 mg of bempedoic acid versus placebo – initiated in January 2016 – is expected to enroll approximately 2,233 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. Additional safety data will be collected in an open-label extension study beyond the specific duration of conduct for Study 1 that was initiated in February 2017.
  • Global Pivotal Phase 3 Study 2 (750 ASCVD and/or HeFH patients): 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. This study is expected to enroll 750 patients with hypercholesterolemia (with ASCVD and/or HeFH) at high CVD risk and whose LDL-C is not adequately controlled with current maximally tolerated lipid-modifying therapies, including high intensity statins. The study will be conducted at approximately 125 sites in the U.S., Canada and Europe. The primary objective is to assess the 12-week LDL-C lowering efficacy of patients treated with bempedoic acid versus placebo. Secondary objectives include evaluating the 24-week LDL-C lowering efficacy, and 52-week safety and tolerability of bempedoic acid versus placebo. Effects on other risk markers, including high sensitivity C-reactive protein (hsCRP), will also be evaluated.
  • Global Pivotal Phase 3 Study 3 (300 patients considered statin intolerant): 24-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. This study is expected to enroll 300 patients with hypercholesterolemia on optimized background lipid-modifying therapy; all patients in this study are considered to be statin intolerant. The study will be conducted at approximately 70 sites in the U.S. and Canada. The primary objective is to assess the 12-week LDL-C lowering efficacy of patients treated with bempedoic acid versus placebo. Secondary objectives include evaluating the 24-week LDL-C lowering efficacy, safety and tolerability of bempedoic acid versus placebo and effects on other risk markers, including hsCRP.
  • Global Pivotal Phase 3 Study 4 (225 patients considered statin intolerant): 12-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 as an add-on to 10 mg of ezetimibe. This study is expected to enroll 225 patients with hypercholesterolemia on optimized background lipid-modifying therapy, including ezetimibe, and patients considered statin intolerant. The study will be conducted at approximately 75 sites in the U.S., Canada and Europe. The primary objective is to assess the 12-week LDL-C lowering efficacy of patients treated with bempedoic acid versus placebo when added to background ezetimibe. Secondary objectives include evaluating safety and tolerability of bempedoic acid when added to ezetimibe, and effects on other risk markers, including hsCRP.

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