Research Summary

Efruxifermin Demonstrates Significant Fibrosis Improvement in Patient with MASH Over 96 Weeks

Kate Young

Key Highlights

  • Efruxifermin demonstrated significantly greater improvements in liver fibrosis compared with placebo at 96 weeks, particularly at the 50 mg dose.
  • Up to 75% of participants receiving 50 mg achieved ≥ 1-stage fibrosis improvement without worsening of MASH.
  • Adverse events were common across groups but generally mild to moderate and not associated with liver injury or death.

Efruxifermin, a bivalent fibroblast growth factor 21 analogue, was associated with marked improvements in fibrosis after 96 weeks of treatment in patients with metabolic dysfunction-associated steatohepatitis (MASH) and stage 2-3 fibrosis. The 50 mg dose achieved the greatest benefit, nearly doubling the response rate compared with placebo.

MASH is a progressive liver disease associated with inflammation and fibrosis that can advance to cirrhosis and hepatic failure. Despite its growing prevalence and burden, effective therapies remain limited, necessitating the development of agents such as efruxifermin with the potential to halt or reverse fibrosis progression.

The HARMONY trial was a multicenter, randomized, double-blind, placebo-controlled, phase 2b study conducted across 41 U.S. academic and community centers. Adults aged 18 to 75 years with biopsy-confirmed MASH and stage F2 or F3 fibrosis were randomized to weekly subcutaneous injections of efruxifermin (28 mg or 50 mg) or placebo. Participants, investigators, and study staff were blinded to group assignment. The primary endpoint was improvement in fibrosis without MASH worsening, assessed initially at week 24 and again at week 96.

Among 128 randomized participants, 126 were included in the modified intention-to-treat analysis. At week 96, 19% of patients receiving placebo, 30% receiving efruxifermin 28 mg, and 49% receiving 50 mg achieved ≥1-stage fibrosis improvement without worsening of MASH. In the biopsy-confirmed subgroup, 24% of placebo recipients improved, compared with 46% in the 28 mg group and 75% in the 50 mg group, with the latter achieving statistical significance (P < .0001). Nearly all participants experienced at least one adverse event, most commonly mild to moderate gastrointestinal symptoms, but no drug-induced liver injury or deaths were reported.

“Efruxifermin resulted in greater improvements in fibrosis than placebo after 96 weeks, warranting further investigation in phase 3 trials,” the study authors concluded.

Reference:
Noureddin M, Frias JP, Neff GW, et al. Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results from a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2025;406(10504):719-730. doi:10.1016/S0140-6736(25)01073-6