Cilofexor does not halt fibrosis progression in noncirrhotic PSC

Treatment with cilofexor in patients with noncirrhotic primary sclerosing cholangitis (PSC) does not appear to reduce the rate of fibrosis progression, according to a phase III study.

A total of 416 adults (62 percent male) with noncirrhotic large-duct PSC were randomly assigned to receive either cilofexor 100 mg (n=277) or placebo (n=139), administered orally once daily for 96 weeks. Histological progression of liver fibrosis, defined as a stage increase of one or more on Ludwig classification, at week 96 was set as the primary endpoint.

The study was terminated prematurely for futility. In 160 patients who had reached 96 weeks of follow-up, analysis indicated a 6.8-percent probability of detecting a significant difference between cilofexor and placebo.

The final analysis of the primary endpoint included 133 patients in the cilofexor group and 64 in the placebo group who had available liver biopsy results. Fibrosis progression occurred in 31 percent of patients in the cilofexor group and in 33 percent in the placebo group at week 96 (treatment difference, −1.4 percent, 95 percent confidence interval [CI], –15.2 to 12.3; p=0.42).

Frequently reported adverse events (AEs) included pruritus (49 percent in the cilofexor group and 36 percent in the placebo group), COVID-19 (23 percent and 19 percent, respectively), and upper abdominal pain (14 percent in each group). Serious AEs occurred in 19 percent of patients each in the cilofexor and placebo groups. There were no treatment-related deaths.