The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.

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Hepatology (Baltimore, Md.)


UDCA; cholestasis; farnesoid X receptor; large duct PSC; primary sclerosing cholangitis


Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a Phase 2 double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor (FXR) agonist in non-cirrhotic patients with large duct PSC. Patients were randomized to receive cilofexor 100 mg (n=22), 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) >1.67xULN and total bilirubin ≤2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with IBD, 46% on UDCA). Baseline median serum ALP and bilirubin were 348 U/L (IQR 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; p=0.029 vs placebo), GGT (-30%;p

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Digestive Health