Akero Therapeutics' efruxifermin shows promise in reversing MASH and fibrosis in Phase 2b trial.

Akero Therapeutics has announced publication of 96-week final results from the Phase 2b HARMONY trial in adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate or advanced fibrosis. Treatment with efruxifermin (EFX) resulted in significant improvements in fibrosis and MASH, with near complete reversal of disease in almost one-third of participants. EFX was generally well tolerated, with a safety profile consistent with previous trials. Confirmation of these benefits is being evaluated in the ongoing Phase 3 SYNCHRONY clinical trial program.

South San Francisco, Calif., July 2, 2025 — Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, has announced the publication of 96-week final results from the Phase 2b HARMONY trial in The Lancet. The study evaluated efruxifermin (EFX) in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and moderate (F2) or advanced (F3) fibrosis.

The publication reports final results from HARMONY, a 96-week multicenter, randomized, double-blind, placebo-controlled trial that enrolled 128 participants. The primary efficacy endpoint was the proportion of participants with at least one stage fibrosis improvement without worsening of MASH. In the modified intent-to-treat (mITT) population at week 96, 49% of participants who received 50mg EFX achieved this endpoint, compared to 19% for placebo (p=0.0030).

Treatment with EFX also resulted in significant improvements in MASH resolution without fibrosis worsening, with 40% and 37% of participants in the 28mg and 50mg EFX groups achieving this endpoint, respectively, compared to 19% for placebo (p=0.020 and p=0.039). A composite endpoint of both MASH resolution and ≥1-stage fibrosis improvement was met by 35% and 28% of participants in the 50mg and 28mg EFX treatment groups, respectively, versus 7% for placebo (p=0.0013 and p=0.0065).

EFX was generally well tolerated, with a safety profile consistent with previous trials. The most frequent adverse events were mild to moderate gastrointestinal events, which occurred at similar rates in the 28mg and 50mg groups. The rate of treatment discontinuation was similar for both doses but was greater than that for placebo. A small reduction in bone mineral density was observed after 96 weeks of EFX treatment.

The sustained reductions in fibrosis and MASH observed in this trial reflect an overall improvement in whole-body metabolic health, as evident by reduced dyslipidemia and increased insulin sensitivity. The magnitude of fibrosis improvement supports the potential of EFX to reduce disease progression and improve clinical outcomes, even in patients with high fibrosis burden.

Confirmation of these potential benefits of EFX is being evaluated in the ongoing Phase 3 SYNCHRONY clinical trial program. EFX, Akero’s lead product candidate for MASH, is currently being evaluated in three ongoing Phase 3 studies.

References:
[1] https://ir.akerotx.com/news-releases/news-release-details/akero-therapeutics-announces-lancet-publication-phase-2b-harmony