Efruxifermin in Compensated Liver Cirrhosis Caused by MASH

This phase 2b randomized, double blind, placebo controlled trial evaluated the efficacy and safety of efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, in 181 patients with compensated cirrhosis (stage 4 fibrosis) caused by MASH. Participants received weekly subcutaneous efruxifermin (28 mg or 50 mg) or placebo for 96 weeks. The primary outcome reduction of ≥1 fibrosis stage without MASH worsening at 36 weeks was not met (13% placebo vs. 18–19% efruxifermin; P=0.52–0.62). However, at 96 weeks, the 50mg dose showed a promising 16-percentage point improvement over placebo (29% vs. 11%; 95% CI, 2 to 30). Efruxifermin also improved noninvasive fibrosis markers (ELF score, liver stiffness) and metabolic parameters (lipids, insulin sensitivity). Adverse events were primarily gastrointestinal (diarrhea, nausea) and mild to moderate. While the primary endpoint was negative, longer-term data suggest potential benefits in fibrosis regression, warranting further phase 3 investigation.

This phase 2b randomized, double blind, placebo controlled trial evaluated the efficacy and safety of efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, in 181 patients with compensated cirrhosis (stage 4 fibrosis) caused by MASH. Participants received weekly subcutaneous efruxifermin (28 mg or 50 mg) or placebo for 96 weeks. The primary outcome reduction of ≥1 fibrosis stage without MASH worsening at 36 weeks was not met (13% placebo vs. 18–19% efruxifermin; P=0.52–0.62). However, at 96 weeks, the 50mg dose showed a promising 16-percentage point improvement over placebo (29% vs. 11%; 95% CI, 2 to 30). Efruxifermin also improved noninvasive fibrosis markers (ELF score, liver stiffness) and metabolic parameters (lipids, insulin sensitivity). Adverse events were primarily gastrointestinal (diarrhea, nausea) and mild to moderate. While the primary endpoint was negative, longer-term data suggest potential benefits in fibrosis regression, warranting further phase 3 investigation.