Farnesoid X receptor agonist Treatment of hepatobiliary and intestinal diseases

Tropifexor (LJN-452) is a highly potent, novel, non-bile acid farnesoid X receptor (FXR) agonist that is currently being evaluated for hepatobiliary and intestinal diseases, particularly nonalcoholic steatohepatitis (NASH), and for primary bile acid diarrhea. In animal models of NASH, tropifexor reduced hepatic fibrosis, inflammation, collagen deposition, serum lipids and liver enzymes. Interim results of clinical trials for NASH showed dose-response increases in fibroblast growth factor 19 (FGF19) and decreases in liver fat content with tropifexor. Significant reductions in liver enzymes were also demonstrated in patients with NASH and primary biliary cholangitis. In primary bile acid diarrhea, tropifexor slowed emptying of ascending colon and increased serum FGF19 and reduced serum 7αC4. Tropifexor appears to be well tolerated with low incidence of pruritus and rare discontinuation due to adverse events. Further phase I and II trials are currently underway and will provide more information on the clinical utility and safety of tropifexor in the treatment of different hepatobiliary and intestinal diseases.