Building a pipeline with innovative medicines at the core

We work hard to lower LDL-C by discovering and developing innovative and combination medicines. 

Cardiovascular Outcomes Trial

Our global cardiovascular outcomes trial (CVOT), called CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen) Outcomes, is a first-of-its-kind, landmark CVOT in patients with statin intolerance to determine the effect of of bempedoic acid on the MACE-4 composite endpoint.

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 1,200 sites in 32 countries.1-3

The CLEAR Outcomes study has now accumulated the targeted 1,620 primary major adverse cardiovascular events (MACE-4) (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) and has met its primary endpoint, demonstrating statistically significant and clinically meaningful results. 

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


  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.

CLEAR Outcomes trial facts

  • Nearly 14,000 patients
  • Completed enrollment in August 2019
  • Comprised of >1,200 sites in 32 countries
  • 48.2% female

Patient characteristics

  • Baseline LDL-C
    o    44.1% <130 mg/dL
    o    33.9% 130-<160 mg/dL
    o    24.0% ≥160 mg/dL
  • Mean subject age at time of enrollment: 65.5±9.0 years
  • Key criteria for enrolled subjects:
    o    Established atherosclerotic cardiovascular disease (ASCVD) or a high risk for developing ASCVD
    o    Documented statin intolerance
    o    LDL-C ≥100 mg/dL on maximally-tolerated lipid-lowering therapy

Primary endpoint

  • Time to first occurrence of any component of the major adverse cardiovascular event composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.

Learn More

Next Gen ACLYi - Investigational Stage

ATP-citrate lyase (ACLY) is an enzyme strategically positioned at the intersection of nutrient catabolism and cholesterol and fatty acid biosynthesis. Esperion Therapeutics is leading the investigation of ACLY biology having brought the first ACLY inhibitor to the market. While preclinical studies and Mendelian randomized trials support a causal role for ACLY in dyslipidemia and ASCVD, they also suggest potential additional effects on metabolism that may benefit other disease states such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)/ non-alcoholic steatohepatitis (NASH)1,2. Furthermore, emerging evidence implicates ACLY as a key metabolic checkpoint utilized by multiple cell types to sense nutrient availability and coordinate metabolic adaptions with cell-specific functions3,4. This expanded understanding has provided key insight into novel connections between chronic positive energy balance and aberrant metabolism and the maladaptation of multiple inflammatory, immune, fibrotic, extra-cellular matrix remodeling, and proliferative processes5-8.

Esperion’s scientific team is exploring this novel insight into ACLY biology. Along with the implementation of leading-edge discovery technology and data science approaches, Esperion aims to reveal new therapeutic opportunities and develop next-generation inhibitors optimized to address multiple life-threatening diseases.

Key Publications and Referencecs:

  1. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis.
    Pinkosky, S., Newton, R., Day, E. et al. Nat Commun 7, 13457 (2016).
  2. Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia.
    Morrow, M., Batchuluun, B., Wu, J., et al. Cell Metabolism 34, 919–936 (2022).
  3. Mendelian Randomization Study of ACLY and Cardiovascular Disease.
    Ference BA, Ray KK, Catapano AL, Ference TB, et al. The New England journal of medicine, 380(11), 1033–1042 (2019).
  4. Targeting ATP-Citrate Lyase in Hyperlipidemia and Metabolic Disorders.
    Pinkosky SL, Groot PHE, Lalwani ND, et al. Trends in molecular medicine, 23(11), 1047–1063 (2017).
  5. A non-canonical tricarboxylic acid cycle underlies cellular identity.
    Arnold, P.K., Jackson, B.T., Paras, K.I. et al. Nature 603, 477–481 (2022).
  6. Lipogenesis inhibitors: therapeutic opportunities and challenges.
    Batchuluun, B., Pinkosky, S.L. & Steinberg, G.R. Nat Rev Drug Discov 21, 283–305 (2022).
  7. Exploring the Role of ATP-Citrate Lyase in the Immune System.
    Dominguez, M., Brüne, B., and Namgaladze, D. Front. Immunol. 12 (2021).
  8. The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming.
    Hochrein, S., Wu, H., Eckstein, M., et al. Cell Metabolism 34, 516–532 (2022).
  9. Sugar addiction: An Achilles’ heel of auto-immune diseases?
    Zaiss, D.M.W., and Coffer, P.J. Cell Metabolism 34, 503-505 (2022).