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 LDL-C–lowering efficacy of bempedoic acid and bempedoic acid plus
ezetimibe fixed-dose combination. The program involves 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 while taking maximally-tolerated statins and ezetimibe, 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.

LDL-C Lowering Indication (Total N=3,600)
CLEAR Harmony (1002-040); N=2230
  • 52 wk
CLEAR Wisdom (1002-047); N=779
  • 52 wk
CLEAR Serenity (1002-046); N=345
  • 24 wk
CLEAR Tranquility (1002-048); N=269
  • 12 wk

All 4 trials were: Randomized | Double blind | Placebo controlled | Parallel group | Multicenter

Phase 3 Clinical Trials

STUDY LDL-C Reduction (percent reduction from baseline, placebo corrected) hsCRP Reduction (median percent change from baseline, placebo corrected) Prevalence of Most Common AEs (≥5%, BA vs placebo for CLEAR studies) Prevalence of Serious AEs (BA vs placebo for CLEAR studies) Discontinuation of IMP Due to AEs (percent, BA vs placebo)
CLEAR Harmony
(1002-040)
(N=2,230)
(BA: n=1,488) (placebo: n=742)
-18.1%
(P<0.001)
-21.5%
(P<0.001)
Nasopharyngitis:
(9.8% vs 11.7%)

Myalgia:
(6.0% vs 6.1%)

12.4%
vs
9.4%
10.9%
vs
7.1%
CLEAR Wisdom
(1002-047)
(N=779)
(BA: n=522)
(placebo: n=257)
-17.4%
(P<0.001)
-8.7%
(P<0.001)
Nasopharyngitis:
(5.2% vs 5.1%)

Urinary tract infection:
(5.0% vs 1.9%)

20.3 %
vs
18.7%
10.9%
vs
8.6%
CLEAR Serenity
(1002-046)
(N=345)
(BA: n=234)
(placebo: n=111)
-21.4%
(P<0.001)
-24.3%
(P<0.001)
Athralgia:
(6.0% vs 4.5%)

Pain in extremity:
(5.6% vs 3.6%)

Myalgia:
(4.7% vs 7.2%)

6.0%
vs
3.6%
18.4%
vs
11.7%
CLEAR Tranquility
(1002-048)
(N=269)
(BA: n=181)
(placebo: n=88)
-28.5%
(P<0.001)
-31.0%
(P<0.001)
Blood uric acid increased:
(7.7% vs 2.3%)
2.8%
vs
3.4%
6.1%
vs
5.7%
Bempedoic Acid + Ezetimibe Fixed-dose Combination
(1002FDC-053)
(N=382)
(BA/EZE: n=108)
(BA: n=110)
(EZE: n=109)
(placebo: n=55)
-29.0%
(P<0.001)
-37.2%
(P<0.001)
Urinary tract infection:
(7.5% for BA/EZE, 2.7% for BA, 2.8% for
EZE, 3.6% for
placebo)

Nasopharyngitis:
(3.7% for BA/EZE, 5.5% for BA, 3.7% for EZE, 1.8% for placebo)

7.5% for
BA/EZE FDC

6.4% for
BA

9.2% for
ezetimibe

1.8% for
placebo

6.5% for
BA/EZE FDC

8.2% for
BA

9.2% for
ezetimibe

3.6% for
placebo

BA = bempedoic acid, EZE = ezetimibe, BA/EZE FDC = bempedoic acid plus ezetimibe fixed-dose combination, AEs = adverse events, IMP = investigational medicinal product

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

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 plans to submit the results to health authorities in 2022, if positive, for inclusion in product labels.

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. The study takes place at more than 1,000 sites in 30 countries. The study is expected to enroll patients 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”).

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