ETC-1002: a future option for lipid disorders?

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.

• Authors: Dragana Nikolic, Dimitri P Mikhailidis, Michael H Davidson, Manfredi Rizzo, Maciej Banach
• Journal: Atherosclerosis (Atherosclerosis) Vol. 237 Issue 2 Pg. 705-10 (Dec 2014) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 25463109 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

• 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