Gemcabene as a Potential Therapeutic for NASH: Lessons Learnt from its Clinical Trials in Dyslipidemia

Elevated hepatic lipogenesis and inflammation are associated with the progression of non-alcoholic steatohepatitis (NASH) and cardiovascular disease. Gemcabene, a small molecule in development for dyslipidemia, reduces plasma very low-density lipoprotein cholesterol (VLDL-C), lowdensity lipoprotein cholesterol (LDL-C), triglycerides (TG) and C-reactive protein (CRP) in animal models and humans. An analysis of the clinical information available for gemcabene and translational research substantiates the potential of gemcabene as a therapeutic agent for NASH. Specifically, gemcabene showed positive effects in clinical trials in severe hypertriglyceridemia and in subsets of obese, diabetic patients, particularly reductions in triglycerides, cholesterol and proatherogenic and inflammation markers. In nonclinical models, gemcabene showed significant improvement in non-alcoholic fatty liver disease (NAFLD) activity and fibrosis scores and affected beneficially the hepatic expression of many lipid regulating and inflammatory genes.

Keywords:Gemcabene; Dyslipidemia; Hypercholesterolemia; Hypertriglyceridemia; Hypertriglyceridemia; Severe hypertriglyceridemia; SHTG; Cardiovascular risk; Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Steatohepatitis; NAFLD; NASH

Abbreviations:TG: Triglycerides; LDL-C: Low –Density Lipoprotein; Non-HDL-C: Non-High-Density Cholesterol; VLDL-C: Very Low-Density Lipoprotein Cholesterol; Apo: apolipoprotein; HSCRP: High-sensitivity C Reactive Protein; SAA: Serum Amyloid A