Building a pipeline with innovative medicines at the core

We work hard to lower LDL-C by discovering and developing innovative and combination medicines. We develop our medicines according to patient preference: oral, once daily and accessible. That means they will be easy to get, easy to take and easy to have. 

Cardiovascular Outcomes Trial

Our global cardiovascular outcomes trial (CVOT), called CLEAR Outcomes, is a first-of-its-kind, landmark CVOT in patients with statin intolerance and is on track to conclude in the second half of 2022.

CLEAR Outcomes is a Phase 3, event-driven, randomized, multicenter, double-blind, placebo-controlled trial designed to evaluate whether treatment with bempedoic acid reduces the risk of cardiovascular events. The primary endpoint of the study is the effect of bempedoic acid on four-component major adverse cardiovascular events (MACE). The study enrolled more than 14,000 patients at over 1,400 sites in 32 countries.1-3

For a comprehensive overview of inclusion and exclusion criteria, and endpoint information, please see the study description on clinicaltrials.gov

What is CLEAR Outcomes?

Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes is a randomized, double-blind, placebo-controlled clinical trial, looking at the effects of bempedoic acid on cardiovascular events for patients with documented statin intolerance and high risk of cardiovascular disease.

CLEAR Outcomes trial facts

  • 14,000+ patients
  • Completed enrollment in August 2019
  • 1,400 sites in 32 countries
  • Largest trial in Esperion’s history

Patient population:

  • Established atherosclerotic cardiovascular disease or diabetes with additional risk factors
  • Documented statin intolerance
  • 47.9% women, 52.1% men
  • Mean age: 65.5±9.0 years
  • LDL cholesterol: 140.7±34.1 mg/dL
    • 42.6% <130 mg/dL
    • 33.1% 130-<160 mg/dL
    • 24.3% ≥160 mg/dL

Primary endpoint

  • Time to four-component major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization

Oral PCSK9 inhibitor

All available PCSK9 treatment options are delivered by injection, but four out of five patients prefer a pill.4 That’s why Esperion is in the investigational stage of developing a small molecule PCSK9 inhibitor that can be taken as a tablet.

PCSK9 (proprotein convertase subtilisin/kexin type 9) is an enzyme responsible for regulating low-density lipoprotein (LDL) receptors. PCSK9 inhibitors stop LDL receptors from being broken down, increasing the number of LDL receptors present to remove cholesterol from the blood. Current approved PCSK9 inhibitors – delivered as injections – have proven to be out of reach for many patients.5,6 A tablet, oral PCSK9 inhibitor would fill a key gap in non-statin treatment options for patients, between statins and shots.

PCSK9 is a validated target for the treatment of dyslipidemia and reduction of cardiovascular risk, with demonstrated efficacy and safety in various high-risk CVD populations.7,8

References: 

1. Esperion completes patient enrollment in the global CLEAR cardiovascular outcomes trial for bempedoic acid [press release]. Ann Arbor, Michigan: Esperion Therapeutics, Inc.; September 5, 2019. Accessed January 16, 2020. 

2. Ruscica M, Banach M, Sahebkar A, Corsini A, Sirtori CR. ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials. Exp Opin Pharmacother. 2019. doi:10.1080/14656566.2019.1583209. 

3. Data on file. Esperion Therapeutics, Inc. 2020.

4. Dibonaventura, M. D., Wagner, J. S., Girman, C. J., Brodovicz, K., Zhang, Q., Qiu, Y., Pentakota, S. R., & Radican, L. (2010). Multinational Internet-based survey of patient preference for newer oral or injectable Type 2 diabetes medication. Patient preference and adherence, 4, 397–406. https://doi.org/10.2147/PPA.S14477 

5. Baum SJ, Toth PP, Underberg JA, Jellinger P, Ross J, Wilemon K (2017). “PCSK9 inhibitor access barriers-issues and recommendations: Improving the access process for patients, clinicians and payers”. Clinical Cardiology. 40 (4): 243–254. doi:10.1002/clc.22713. PMC 5412679. PMID 28328015. 

6. Gina Kolata, “These Cholesterol-Reducers May Save Lives. So Why Aren’t Heart Patients Getting Them?”, The New York Times, Oct. 2, 2018. Retrieved 18 December 2020. 

7. Sabatine MS et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376:1713-1722. DOI: 10.1056/NEJMoa1615664. https://www.nejm.org/doi/full/10.1056/nejmoa1615664 

8. Schwartz, GG et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379:2097-2107. DOI: 10.1056/NEJMoa1801174. https://www.nejm.org/doi/full/10.1056/NEJMoa1801174