A RECENT Phase IIb clinical trial has evaluated the effectiveness and safety of efruxifermin in patients with biopsy-confirmed compensated cirrhosis resulting from metabolic dysfunction–associated steatohepatitis (MASH), a progressive liver disease often linked to obesity and Type 2 diabetes. Efruxifermin is a bivalent analogue of fibroblast growth factor 21 (FGF21), a hormone involved in regulating metabolism, and has previously shown promise in improving liver fibrosis in earlier-stage MASH. However, its performance in patients with more advanced liver damage, such as Stage 4 fibrosis or cirrhosis, has remained unclear until now.
In this double-blind, placebo-controlled trial, 181 participants were randomised to receive weekly injections of either 28 mg or 50 mg of efruxifermin or a placebo. The trial’s primary goal was to assess whether the drug could reduce liver fibrosis by at least one stage without worsening MASH symptoms over 36 weeks. Secondary outcomes were measured at 96 weeks. Liver biopsies were carried out to evaluate treatment effects.
At the 36-week mark, improvements in fibrosis were modest and not statistically significant. Only 13% of patients in the placebo group, 18% in the 28 mg group, and 19% in the 50 mg group showed any improvement in fibrosis without MASH progression. Differences between treatment and placebo groups were small, with wide confidence intervals and no statistically significant benefit.
However, results at 96 weeks showed a more encouraging trend. The proportion of patients with reduced fibrosis increased to 21% in the 28 mg group and 29% in the 50 mg group, compared with 11% in the placebo group. While the lower dose still did not achieve statistical significance, the higher dose demonstrated a 16 percentage point improvement over placebo, suggesting potential long-term benefit.
Gastrointestinal side effects were more common in those receiving efruxifermin but were generally mild or moderate. Overall, the findings suggest efruxifermin may offer delayed therapeutic benefits for patients with MASH-related cirrhosis, although longer-term studies are needed to confirm its clinical value.
Reference
Noureddin M et al. Efruxifermin in compensated liver cirrhosis caused by MASH. N Engl J Med. 2025;DOI:10.1056/NEJMoa2502242.
