Tackling MASH: A Silent Epidemic

On November 8, 2024, Akero Therapeutics reported its third-quarter financial results and announced a major milestone: the first patient has been dosed in its Phase 3 SYNCHRONY Outcomes study for efruxifermin (EFX), a novel treatment for metabolic dysfunction-associated steatohepatitis (MASH). Formerly known as NASH, MASH is a progressive liver disease affecting millions globally, with no approved therapies to date.

Akero’s SYNCHRONY program now includes three active Phase 3 trials:

• SYNCHRONY Outcomes: For patients with compensated cirrhosis (F4)
• SYNCHRONY Histology: For pre-cirrhotic patients (F2-F3)
• SYNCHRONY Real-World: Observational study to support broader clinical utility

This comprehensive strategy positions Akero as a front-runner in the race to deliver a first-in-class therapy for MASH.

EFX: A Dual-Action Metabolic Modulator

EFX is a fibroblast growth factor 21 (FGF21) analog, designed to improve liver histology and metabolic parameters. Its mechanism includes:

• Reducing liver fat and inflammation
• Improving insulin sensitivity and lipid profiles
• Promoting fibrosis regression

In earlier Phase 2b trials, EFX showed significant improvements in liver fibrosis and resolution of MASH after 96 weeks of treatment. The Phase 3 trials aim to confirm these findings in larger, more diverse populations.

Trial Design Highlights

Here’s how Akero’s Phase 3 trials are structured:

Patients receive weekly injections of either EFX 28mg, EFX 50mg, or placebo. The trials are randomized and placebo-controlled, with histology endpoints based on liver biopsies.

Scaling for Impact

Akero is preparing for potential commercialization by:

• Expanding manufacturing capacity for EFX
• Engaging with regulatory agencies for accelerated approval pathways
• Building partnerships with hepatology centers and patient advocacy groups
• Exploring combination therapies with GLP-1 agonists and other metabolic agents

If successful, EFX could become the first approved treatment for MASH, a condition that affects up to 5% of the global population and is a leading cause of liver transplantation.

Looking Ahead: A New Era in Liver Disease

Akero’s progress marks a turning point in the fight against MASH. With robust clinical data, strategic trial design, and growing investor confidence, the company is poised to deliver a transformative therapy for a disease long overlooked.