ETC-1002: a future option for lipid disorders?

Atherosclerosis. 2014 Dec;237(2):705-10. doi: 10.1016/j.atherosclerosis.2014.10.099. Epub 2014 Oct 31.

Abstract

ETC-1002 is a new investigational low density lipoprotein cholesterol (LDL-C)-lowering agent (Esperion Therapeutics, Inc.). ETC-1002 is a dicarboxylic acid derivative with a novel mechanism of action targeting two hepatic enzymes--adenosine triphosphate-citrate lyase (ACL) and adenosine monophosphate-activated protein kinase (AMPK), inhibiting sterol and fatty acid synthesis and promoting mitochondrial long-chain fatty acid oxidation. This agent is currently in phase II clinical research. Available data report that ETC-1002 significantly decreased LDL-C levels (up to 32%) in both patients with normal and elevated baseline levels of triglycerides. Such beneficial effect is superior to currently approved non-statin lipid lowering agents. The levels of apolipoprotein B (apoB) and non-high density lipoprotein cholesterol (non-HDL-C) were also reduced with beneficial effect on other cardiometabolic factors such as inflammatory markers, blood pressure and body weight. Although, the safety and tolerability of ETC-1002 needs to be confirmed in ongoing and future, larger studies, this agent has, so far, been generally safe and well tolerated. This novel, oral, once-daily, small molecule may lead to effective LDL-C lowering treatment in hypercholesterolaemic subjects who are statin intolerant or as add-on therapy in those who are unable to reach the LDL-C goals despite being on statin therapy. This agent might not only exert lipid-lowering related benefits, but also favourable cardiometabolic effects.

Keywords: Cardiometabolic risk; ETC-1002; Lipid lowering therapy; Low density lipoprotein cholesterol.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • ATP Citrate (pro-S)-Lyase / metabolism
  • Animals
  • Apolipoproteins B / metabolism
  • Blood Pressure
  • Body Weight
  • Cholesterol, LDL / drug effects*
  • Clinical Trials, Phase II as Topic
  • Dicarboxylic Acids / therapeutic use*
  • Disease Models, Animal
  • Fatty Acids / therapeutic use*
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / therapeutic use
  • Liver / enzymology
  • Mice
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Rats

Substances

  • Apolipoproteins B
  • Cholesterol, LDL
  • Dicarboxylic Acids
  • Fatty Acids
  • Hypolipidemic Agents
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • ATP Citrate (pro-S)-Lyase
  • AMP-Activated Protein Kinases