fenofibrate + firsocostat

Fenofibrate + firsocostat is an investigational combination therapy studied primarily for the treatment of nonalcoholic steatohepatitis (NASH), particularly in patients with advanced fibrosis and hypertriglyceridemia. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist that alters lipid metabolism by increasing lipolysis, activating lipoprotein lipase, and reducing apoprotein C-III levels. Firsocostat (GS-0976) is a small molecule inhibitor of acetyl-CoA carboxylase (ACC), which catalyzes de novo hepatic lipogenesis and regulates fatty acid oxidation. ACC inhibition by firsocostat reduces liver fat but can increase plasma triglycerides; fenofibrate co-administration mitigates this effect by improving lipid profiles. The combination has shown efficacy in reducing hepatic steatosis, improving liver biochemistry, and preventing increases in triglycerides associated with ACC inhibition in NASH patients[1][2][5][7].