TOPLINE

In patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced (F2/F3) fibrosis or compensated cirrhosis, efruxifermin 50 mg was associated with improved fibrosis response rates compared with placebo. Among a majority of early fibrosis responders in the efruxifermin group, improvements persisted through week 96. 

METHODOLOGY

• MASH is a progressive liver disease involving hepatic fat accumulation that may advance to cirrhosis and liver failure. Efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, is being developed as a treatment for MASH.
• Researchers conducted two multicenter, randomized controlled phase 2b trials lasting 96 weeks each: HARMONY, which included patients with MASH and F2/F3 fibrosis (n = 126), and SYMMETRY, which included patients with MASH and compensated cirrhosis (n = 181). The trials assessed improvement in liver fibrosis with efruxifermin over time.
• Participants were randomly assigned 1:1:1 to receive either efruxifermin 28 mg, efruxifermin 50 mg, or placebo — all given subcutaneously once a week.
• The primary histology endpoint was fibrosis response, defined as ≥ 1-stage improvement in fibrosis without worsening of MASH. Liver biopsies were performed at baseline, week 24 (in HARMONY) or week 36 (in SYMMETRY), and week 96.
• Liver stiffness and enhanced liver fibrosis were also assessed.  

TAKEAWAY

• Among participants with a biopsy at week 24 in the HARMONY trial (n = 113), fibrosis response rates were 20% for placebo compared with 39% for efruxifermin 28 mg (P < .05) and 41% for efruxifermin 50 mg (P < .05).
• Among those with biopsy at 96 weeks (n = 88), fibrosis response rates were 24% with placebo vs 75% with efruxifermin 50 mg (P < .001) and 46% with efruxifermin 28 mg (not significant). Among those receiving efruxifermin 50 mg who had responded by week 24, 92% maintained their response at week 96.
• In the SYMMETRY trial, among participants with a biopsy at week 36 (n = 154), fibrosis response rates were 14% with placebo, 22% with efruxifermin 28 mg, and 24% for efruxifermin 50 mg (not significant); by week 96 (n = 134), the response rates were 15% with placebo vs 39% with efruxifermin 50 mg (P < .01) and 29% with efruxifermin 28 mg (not significant).
• Efruxifermin 50 mg was associated with significant improvements in liver stiffness compared with placebo by week 96 in both trials (P < .05). Efruxifermin was well tolerated. Gastrointestinal symptoms and administration site reactions represented the most frequent adverse events with efruxifermin, with most being mild-to-moderate.

IN PRACTICE

"In participants with MASH and F2/F3 fibrosis or cirrhosis, efruxifermin was associated with rapid fibrosis improvements, indicating a direct hepatic antifibrotic effect. Larger fibrosis improvements were observed by histology and noninvasive measures by end of study. Phase 3 trials of efruxifermin in MASH are ongoing," the authors wrote.

SOURCE

The study was led by Arun J. Sanyal, MD, Virginia Commonwealth University in Richmond, Virginia. It was presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.

LIMITATIONS

No limitations were discussed in the abstract. 

DISCLOSURES

Three authors reported being employees of, and holding stock options in, Akero Therapeutics, a Novo Nordisk company. Other authors reported consulting relationships, advisory board roles, holding stock options, or receiving grant/research support or royalties from multiple companies including Akero Therapeutics. One of the authors also reported being the principal investigator for a drug study with multiple companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.