Akero Therapeutics’ Efruxifermin Shows Breakthrough Fibrosis Reversal in MASH Cirrhosis: A Game-Changer for Liver Disease?

The liver disease landscape is on the cusp of a major shift, and Akero Therapeutics (NASDAQ: AKRO) is at the forefront with its Phase 2b SYMMETRY trial results for efruxifermin. Presented at the EASL Congress 2025, the data reveal a transformative potential for patients with metabolic dysfunction-associated steatohepatitis (MASH) and compensated cirrhosis—a population with a 50% five-year mortality rate and no approved therapies to reverse fibrosis. Here’s why investors should take notice.

The Unmet Need: MASH and Cirrhosis

MASH, a liver disease driven by metabolic dysfunction, affects millions worldwide. In its most advanced stage—compensated cirrhosis (F4)—scarring of the liver becomes irreversible, leading to life-threatening complications like liver failure or cancer. Until now, no treatment has demonstrated the ability to reverse fibrosis in this population. Akero’s efruxifermin, a weekly FGF21 analog, is now the first therapy to cross this critical threshold.

SYMMETRY Trial Results: A Landmark Achievement

The Phase 2b trial enrolled 182 patients with biopsy-confirmed MASH-related cirrhosis. Key findings include:
- Fibrosis Improvement Without MASH Worsening:
- At 96 weeks, 39% of patients on the 50mg dose achieved ≥1-stage fibrosis improvement versus 15% on placebo (p=0.009).
- In an intent-to-treat analysis (accounting for missing data), 29% of EFX-treated patients improved versus 11% on placebo (p=0.031).
- The treatment effect doubled between Week 36 and 96, highlighting the need for prolonged therapy in advanced cirrhosis.
- Consistency Across Subgroups:
- Benefits were consistent in patients with type 2 diabetes and those on GLP-1 medications, broadening its applicability.
- Among patients not using GLP-1 therapies, 45% on EFX improved versus 17% on placebo (p=0.009).

Non-Invasive Biomarkers and Safety

• ELF Score: A biomarker of fibrosis decreased by -0.53 in the 50mg group versus +0.22 in placebo (p<0.001).
• Liver Stiffness (FibroScan): Reduced by 24% in EFX vs. 8% in placebo (p<0.05).
• Safety: Mild gastrointestinal side effects (diarrhea, nausea) were common but transient. No treatment-related deaths occurred, contrasting with one placebo-related fatality from pneumonia.

Market Opportunity and Regulatory Path

The global market for NASH/MASH therapies is projected to reach $26 billion by 2030, driven by rising metabolic disorders. Efruxifermin’s ability to reverse fibrosis in the most severe stage positions it as a first-in-class therapy.

Akero plans to advance EFX into Phase 3 trials under the SYNCHRONY program, including:
1. SYNCHRONY Outcomes: A >1,000-patient trial assessing clinical endpoints (e.g., hepatic decompensation, mortality) in compensated cirrhosis.
2. SYNCHRONY Histology: Targeting pre-cirrhotic patients (F2-F3 fibrosis).

Risks and Considerations

• Regulatory Hurdles: The FDA requires Phase 3 trials to confirm clinical benefits, not just histological improvements.
• Competition: Other NASH therapies (e.g., resmetirom, elafibranor) focus on earlier-stage fibrosis. EFX’s cirrhosis focus may carve a niche, but rivals like Novo Nordisk’s semaglutide (a GLP-1 agonist) are also being studied in MASH.
• Long-Term Data: While the 96-week data are encouraging, durability beyond two years remains untested.

Conclusion: A High-Reward, High-Risk Play

Akero’s SYMMETRY trial represents a paradigm shift in liver disease treatment. With no approved therapies for MASH-related cirrhosis, efruxifermin’s 39% fibrosis improvement rate—doubling over time—creates a compelling value proposition. If Phase 3 trials succeed, Akero could capture a significant share of a multi-billion-dollar market.

However, investors should weigh the risks. The stock could face volatility pending Phase 3 results, and regulatory approval is far from certain. Still, for those willing to bet on a first-in-class therapy addressing a deadly unmet need, Akero’s efruxifermin deserves attention. With a current market cap of $1.2 billion, the company’s valuation may climb if the drug meets its Phase 3 milestones.

The SYMMETRY data underscores a critical truth: for the millions living with advanced MASH, time is running out. If efruxifermin delivers on its promise, it could redefine survival odds—and Akero’s future.

Data Sources: EASL 2025 Congress presentations, Akero Therapeutics investor materials, GlobalData estimates.