ETC-1002: A future option for lipid disorders?

• Published in: Atherosclerosis Vol. 237; no. 2; pp. 705 - 710
• Main Authors: Nikolic, Dragana, Mikhailidis, Dimitri P., Davidson, Michael H., Rizzo, Manfredi, Banach, Maciej
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.12.2014
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Apolipoproteins B - metabolism; ATP Citrate (pro-S)-Lyase - metabolism; Blood Pressure; Body Weight; Cardiometabolic risk; Cardiovascular; Cholesterol, LDL - drug effects; Clinical Trials, Phase II as Topic; Dicarboxylic Acids - therapeutic use; Disease Models, Animal; ETC-1002; Fatty Acids - therapeutic use; Humans; Hypercholesterolemia - drug therapy; Hyperlipidemias - drug therapy; Hypolipidemic Agents - therapeutic use; Lipid lowering therapy; Liver - enzymology; Low density lipoprotein cholesterol; Mice; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Rats; ETC-1002; Lipid lowering therapy; Cardiometabolic risk; Low density lipoprotein cholesterol
• DOI: 10.1016/j.atherosclerosis.2014.10.099
• ISSN: 0021-9150; 1879-1484

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. [Display omitted] •ETC-1002 is a new investigational LDL-C-lowering agent (Esperion Therapeutics Inc.).•This agent is currently in phase II clinical research.•ETC-1002 targets two hepatic enzymes – ACL and AMPK.•It significantly reduces LDL-C (up to 32%) independently of TGs baseline levels.•It needs to be confirmed, but ETC-1002 has been generally safe and well tolerated.