Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Oct;18(10):61.
doi: 10.1007/s11883-016-0611-4.

Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase

Ozlem Bilen  1   2 , Christie M Ballantyne  3   4   5
Affiliations
Review

Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase

Ozlem Bilen et al. Curr Atheroscler Rep. 2016 Oct.

Abstract

Bempedoic acid (ETC-1002), a novel therapeutic approach for low-density lipoprotein cholesterol (LDL-C) lowering, inhibits ATP citrate lyase (ACL), an enzyme involved in fatty acid and cholesterol synthesis. Although rodent studies suggested potential effects of ACL inhibition on both fatty acid and cholesterol synthesis, studies in humans show an effect only on cholesterol synthesis. In phase 2 studies, ETC-1002 reduced LDL-C as monotherapy, combined with ezetimibe, and added to statin therapy, with LDL-C lowering most pronounced when ETC-1002 was combined with ezetimibe in patients who cannot tolerate statins. Whether clinically relevant favorable effects on other cardiometabolic risk factors such as hyperglycemia and insulin resistance occur in humans is unknown and requires further investigation. Promising phase 2 results have led to the design of a large phase 3 program to gain more information on efficacy and safety of ETC-1002 in combination with statins and when added to ezetimibe in statin-intolerant patients.

Keywords: ETC-1002; Low-density lipoprotein cholesterol.

PubMed Disclaimer

Conflict of interest statement

Ozlem Bilen declares no conflict of interest. Christie M. Ballantyne declares consultant fees, grants, and research support from Esperion, paid to her institution, during the conduct of the study; she also declares grants, research support, and/or consultant fees from Amarin, Amgen, Eli Lilly, Otsuka, Novartis, Pfizer, Regeneron, Sanofi-Synthelabo, Takeda, National Institutes of Health, American Heart Association, and American Diabetes Association; she also declares consultant fees from AstraZeneca, Ionis, Genzyme, Matinas BioPharma, and Merck. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Major metabolic pathways affected by bempedoic acid (ETC-1002) in humans as supported by clinical trial data. Animal data suggested additional effects on triglyceride metabolism via ACL inhibition and other cardiometabolic pathways via AMP-activated protein kinase (AMPK) activation. ACL ATP citrate lyase, Acetyl-CoA acetyl coenzyme A, HMG-S HMG-CoA synthase, HMG-R HMG-CoA reductase
See this image and copyright information in PMC

References

    1. Kolansky DM. Acute coronary syndromes: morbidity, mortality, and pharmacoeconomic burden. Am J Manag Care. 2009;15:S36–41. - PubMed
    1. Wiviott SD, Cannon CP, Morrow DA, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46:1411–1416. doi: 10.1016/j.jacc.2005.04.064. - DOI - PubMed
    1. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711–1718. doi: 10.1001/jama.285.13.1711. - DOI - PubMed
    1. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307–1316. doi: 10.1001/jama.292.11.1307. - DOI - PubMed
    1. Virani SS, Woodard LD, Akeroyd JM, et al. Is high-intensity statin therapy associated with lower statin adherence compared with low- to moderate-intensity statin therapy? Implications of the 2013 American College of Cardiology/American Heart Association Cholesterol Management Guidelines. Clin Cardiol. 2014;37:653–659. doi: 10.1002/clc.22343. - DOI - PMC - PubMed

MeSH terms