Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase.
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.
Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.|Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
Ozlem
O
Bilen
Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. cmb@bcm.edu.|Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. cmb@bcm.edu.|Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. cmb@bcm.edu.
Christie M
CM
Ballantyne
D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use; D005227:Fatty Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C581236:8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; D001275:ATP Citrate (pro-S)-Lyase; D000069438:Ezetimibe
ETC-1002; Low-density lipoprotein cholesterol
Metabolism. 2014 Jul;63(7):895-902
24814684
J Lipid Res. 2013 Aug;54(8):2095-108
23709692
Arch Intern Med. 2012 Jan 23;172(2):144-52
22231607
JAMA. 2004 Sep 15;292(11):1307-16
15337732
Biochem J. 1990 Nov 15;272(1):181-6
2176080
Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):676-83
24385236
J Clin Lipidol. 2016 May-Jun;10(3):556-67
27206943
J Am Coll Cardiol. 2005 Oct 18;46(8):1411-6
16226163
Clin Cardiol. 2014 Nov;37(11):653-9
25324147
J Am Coll Cardiol. 2013 Sep 24;62(13):1154-62
23770179
Biochim Biophys Acta. 1968 Apr 16;158(1):51-61
5652435
Am J Manag Care. 2009 Mar;15(2 Suppl):S36-41
19355807
J Clin Lipidol. 2015 Jul-Aug;9(4):525-32
26228670
J Clin Lipidol. 2015 May-Jun;9(3):295-304
26073387
PLoS One. 2013 Apr 09;8(4):e47681
23593110
Curr Opin Lipidol. 2007 Aug;18(4):401-8
17620856
J Lipid Res. 2010 Sep;51(9):2516-26
20488800
Biochem J. 1998 Aug 15;334 ( Pt 1):113-9
9693110
J Clin Lipidol. 2015 May-Jun;9(3):384-9
26073398
Lipids. 1977 Jan;12(1):1-9
834114
QJM. 2012 Feb;105(2):145-57
21920996
J Lipid Res. 2013 Jan;54(1):134-51
23118444
JAMA. 2001 Apr 4;285(13):1711-8
11277825