Efruxifermin Fails to Significantly Reduce Fibrosis in Compensated Cirrhosis: Study
According to a new study published in The New England Journal of Medicine, efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, failed to significantly lower fibrosis in individuals with compensated cirrhosis due to metabolic dysfunction associated steatohepatitis (MASH). Although it had been promising in previous trials for stage 2 or stage 3 fibrosis, the effectiveness of efruxifermin in patients with advanced fibrosis (stage 4) was unclear. This phase 2b, randomized, double-blind, placebo-controlled trial was conducted by Mazen N. and colleagues.
The trial involved 181 patients with biopsy-proven compensated cirrhosis due to MASH (stage 4 fibrosis). Patients were randomly assigned to receive weekly subcutaneous efruxifermin (28 mg or 50 mg) or placebo. The main outcome was regarded as a decrease by at least one stage of fibrosis without MASH deterioration at 36 weeks. Secondary outcomes were fibrosis decrease at 96 weeks. Liver biopsy was done in 154 patients at 36 weeks and in 134 patients at 96 weeks.
Key Findings
Reduction in fibrosis without MASH worsening at 36 weeks in:
• 13% of placebo patients (8 of 61 patients).
• 18% of patients receiving 28-mg efruxifermin (10 of 57 patients).
• 19% of patients receiving 50-mg efruxifermin (12 of 63 patients).
At 96 weeks, reduction of fibrosis without worsening of MASH was observed in:
• 11% of patients in the placebo group (7 of 61 patients).
• 21% of patients in the 28-mg efruxifermin group (12 of 57 patients).
• 29% of patients in the 50-mg efruxifermin group (18 of 63 patients).
• The between-group difference in fibrosis reduction at 96 weeks between the 50-mg efruxifermin group and placebo was 16 percentage points (95% CI, 2 to 30).
• Gastrointestinal adverse events were more common in patients receiving efruxifermin, but most were mild or moderate.
Efruxifermin failed to significantly lower fibrosis in patients with MASH-induced compensated cirrhosis. More gastrointestinal adverse events were seen in the efruxifermin arms, but these were generally mild or moderate in severity. The findings indicate that although efruxifermin might have some promise, its place in treating advanced fibrosis in MASH is unclear.
Reference:
Noureddin, M., Rinella, M. E., Chalasani, N. P., Neff, G. W., Lucas, K. J., Rodriguez, M. E., Rudraraju, M., Patil, R., Behling, C., Burch, M., Chan, D. C., Tillman, E. J., Zari, A., de Temple, B., Shringarpure, R., Jain, M., Rolph, T., Cheng, A., & Yale, K. (2025). Efruxifermin in compensated liver cirrhosis caused by MASH. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2502242