Akero Therapeutics (AKRO) 43rd Annual J.P. Morgan Healthcare Conference 2025 summary

Key clinical progress and trial updates

• Efruxifermin (EFX) advanced from phase 2b to phase 3 with the SYNCHRONY program, including three studies targeting a broad spectrum of liver fibrosis stages, with first patients enrolled in Q4 2023 and double-blind enrollment completed in January 2025.

• SYNCHRONY Real World, a non-invasive phase 3 study, completed enrollment of 601 patients and will read out in H1 2026; SYNCHRONY Histology readout expected H1 2027.

• Phase 2b HARMONY and SYMMETRY studies showed significant fibrosis improvement and MASH resolution, especially with 50mg EFX at 96 weeks, with 75% of patients at 50mg showing one-stage improvement.

• Phase 2b Symmetry trial for cirrhotic (F4) patients showed 24% one-stage fibrosis improvement at 50mg, though not statistically significant vs. placebo.

• Non-invasive measures (ELF, FibroScan) and biomarkers correlated well with histologic improvements, supporting future clinical monitoring.

Efruxifermin mechanism and clinical impact

• Efruxifermin is a bivalent FGF21 analog with extended half-life and high B-Klotho affinity, designed for once-weekly dosing and enhanced receptor binding.

• Demonstrated sustained pharmacodynamic effects and potential to reverse fibrosis, including rare three-stage improvements in some patients.

• Efficacy observed in both pre-cirrhotic (F2/F3) and cirrhotic (F4) populations, with robust response rates in harder-to-treat F3 patients.

• Placebo-adjusted effect sizes among the best in the field, despite statistical challenges in biopsy-based endpoints; EFX's fibrosis improvement rates are competitive with or exceed other investigational therapies for MASH cirrhosis.

• No investigational drug has yet reported statistically significant fibrosis improvement without worsening of MASH in cirrhosis patients.

Safety, tolerability, and patient management

• Efruxifermin was generally well tolerated; most adverse events were GI-related, mild to moderate, with low discontinuation rates (<10% over two years).

• No significant changes in blood pressure, hematologic, or liver function markers; bone mineral density reductions observed at two years, especially at higher dose.

• Fracture rates were similar across groups; vertebral fractures only in placebo.

• Emphasis on improving bone safety and standard-of-care supplementation in future studies.

• Patient retention in cirrhotic trials supported by open-label extension and lack of alternative therapies.