Efruxifermin Shows Durable Antifibrotic Response in MASH Through 96 Weeks

Most participants with metabolic dysfunction-associated steatohepatitis (MASH) who achieved an early fibrosis response to efruxifermin 50 mg maintained it through 96 weeks, according to findings from analyses of the phase 2b HARMONY and SYMMETRY trials presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee. Additional participants responded for the first time by week 96, and fibrosis response rates rose in both moderate to advanced fibrosis and compensated cirrhosis.1

Efruxifermin Fibrosis Response Over Time in HARMONY and SYMMETRY

Efruxifermin is a bivalent Fc-fibroblast growth factor 21 (FGF21) analog with balanced agonism of FGF receptors 1c, 2c, and 3c. No therapies are approved for MASH with compensated cirrhosis, and the primary 96-week results of both trials have been published.1,3 The new analysis, led by Arun Sanyal, MD, Virginia Commonwealth, examined the time course of fibrosis improvement to assess whether efruxifermin exerts a direct antifibrotic effect.1

HARMONY randomly assigned 126 adults with biopsy-confirmed MASH and F2 or F3 fibrosis, and SYMMETRY randomly assigned 181 adults with compensated cirrhosis (F4c).1 Participants in both trials received once-weekly subcutaneous efruxifermin 28 mg, efruxifermin 50 mg, or placebo in a 1:1:1 ratio for 96 weeks. Liver biopsies were obtained at baseline, at week 24 (HARMONY) or week 36 (SYMMETRY), and at week 96.1

HARMONY participants had a mean age of 55 years and a mean BMI of 38 kg/m²; 70% had type 2 diabetes and 66% had F3 fibrosis. SYMMETRY participants had a mean age of 61 years and a mean BMI of 36 kg/m², and 80% had type 2 diabetes.1

Among HARMONY participants with a week 24 biopsy (n = 113), fibrosis improvement of at least one stage without MASH worsening occurred in 20% with placebo, 39% with efruxifermin 28 mg, and 41% with efruxifermin 50 mg (both P <.05).¹ At week 96 (n = 88), response rates were 24%, 46% (not significant), and 75% (P <.001), respectively. In the 50-mg group, 11 of 12 week 24 responders (92%) maintained their response at week 96.1

Efruxifermin in Compensated MASH Cirrhosis, Noninvasive Fibrosis Tests, and Safety

In SYMMETRY, fibrosis response at week 36 (n = 154) did not differ significantly from placebo (14% vs 22% and 24%). By week 96 (n = 134), response rates reached 15% with placebo, 29% with 28 mg (not significant), and 39% with 50 mg (P < .01). Among 50-mg week 36 responders, nine of 12 (75%) maintained their response at week 96.1

The published SYMMETRY report noted the week 36 primary end point was not met; in the full randomized population, week 96 response rates were 11%, 21%, and 29%.3 The ACG analysis reports rates among participants with biopsies at each time point.1

Liver stiffness by vibration-controlled transient elastography improved significantly with efruxifermin 50 mg vs placebo at week 96 in both trials (P <.05). Mean baseline values were 14.8 kPa in HARMONY and 24.4 kPa in SYMMETRY.1 Enhanced liver fibrosis (ELF) scores improved with both doses at the interim biopsy time point and at week 96 (all P < .05 vs placebo).1

The most common adverse events (AEs) were gastrointestinal, mostly mild to moderate, and transient. Diarrhea occurred in 44% and 54% of participants receiving 50 mg in HARMONY and SYMMETRY, respectively, vs 30% with placebo in each trial. AEs led to discontinuation in 7% and 17% of the 50-mg groups, compared with 0% and 3% with placebo.1

Investigators reported small but statistically significant reductions in bone mineral density at week 96, with no increase in fractures and no drug-induced liver injury. Increased appetite was more frequent with efruxifermin, although mean body weight was generally unchanged.1

The investigators concluded the early and sustained responses support a direct hepatic antifibrotic effect of efruxifermin. Phase 3 trials are enrolling participants with F2/F3 MASH (NCT06215716; 28 mg and 50 mg) and compensated cirrhosis (NCT06528314; 50 mg).1

References

1. Sanyal A, Behling C, Bedossa P, et al. Efruxifermin induced a rapid and direct antifibrotic response that was sustained through 96 weeks in phase 2b trials of participants with MASH and F2/F3 fibrosis or cirrhosis. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 13, 2026; Nashville, TN.

2. 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

3. Noureddin M, Rinella ME, Chalasani NP, et al. Efruxifermin in compensated liver cirrhosis caused by MASH. N Engl J Med. 2025;392(24):2413-2424. doi:10.1056/NEJMoa2502242