8-K: Akero Therapeutics Announces Positive Phase 2b Results for Efruxifermin in MASH Cirrhosis

Akero Therapeutics reports statistically significant reversal of compensated cirrhosis due to MASH with its drug candidate efruxifermin (EFX) in a Phase 2b study.

Summary

• Akero Therapeutics announced preliminary topline results from its Phase 2b SYMMETRY study, evaluating efruxifermin (EFX) in patients with compensated cirrhosis due to MASH.
• The study showed that 39% of patients treated with 50mg of EFX experienced reversal of cirrhosis with no worsening of MASH, compared to 15% in the placebo group, in the primary analysis of patients with baseline and week 96 biopsies.
• In the Intent-to-Treat (ITT) analysis, 29% of patients in the 50mg EFX group experienced reversal of cirrhosis, compared to 12% in the placebo group.
• The study also demonstrated improvements in non-invasive measures of liver fibrosis and injury, such as ELF score and liver stiffness.
• EFX was generally well-tolerated, with most adverse events being mild to moderate gastrointestinal issues.
• The company had approximately $800 million in cash, cash equivalents, and marketable securities as of December 31, 2024.

Sentiment

Score: 9

Explanation: The document presents highly positive clinical trial results, demonstrating a significant breakthrough in the treatment of MASH-related cirrhosis. The strong efficacy data, coupled with a favorable safety profile and a solid cash position, makes this a very positive announcement from an investment perspective.

Positives

• Efruxifermin (EFX) demonstrated a statistically significant reversal of cirrhosis in patients with MASH, a first for any compound in this space.
• The effect size of EFX more than doubled from week 36 to week 96, indicating a sustained and improved response with longer treatment.
• The reversal of cirrhosis was observed even in patients not taking GLP-1 therapy, suggesting the effect is independent of GLP-1 use.
• EFX showed improvements in non-invasive markers of liver fibrosis and injury, supporting the histological findings.
• The drug was generally well-tolerated, with no drug-related serious adverse events reported.
• The company has a strong cash position of approximately $800 million, providing financial stability for ongoing and future trials.

Negatives

• Some patients experienced mild to moderate gastrointestinal side effects such as diarrhea, nausea, and increased appetite.
• There was one death in the placebo arm due to pneumonia, although this was not related to the study drug.
• There was a small reduction in bone mineral density observed in the 50mg EFX group, although this was comparable to that seen with GLP-1 treatments.

Risks

• The reported results are preliminary and subject to change upon completion of the company's financial statement closing procedures and audit.
• Positive results from this study may not necessarily predict the results of future or ongoing clinical studies.
• The company's ability to fund operations and execute its strategy is subject to risks and uncertainties.
• Regulatory developments in the United States and foreign countries could impact the approval and commercialization of EFX.
• There is a risk of competition from other companies developing treatments for MASH.

Future Outlook

The company plans to continue evaluating 50mg EFX in its ongoing Phase 3 SYNCHRONY Outcomes study in patients with compensated cirrhosis due to MASH, and is actively enrolling patients in all three SYNCHRONY studies. The company expects to report results for the SYNCHRONY Real-World study in the first half of 2026 and for the SYNCHRONY Histology study in the first half of 2027.

Management Comments

• Mazen Nourredin, M.D., stated that there is now reason to be optimistic about the future potential of EFX as a much-needed treatment for cirrhosis.
• Andrew Cheng, M.D., Ph.D., said that the report of reversal of cirrhosis due to MASH sets EFX apart from other treatments in the MASH landscape.

Industry Context

This announcement is significant as it reports the first statistically significant reversal of cirrhosis due to MASH, a major unmet need in the treatment of liver disease. This positions Akero's EFX as a potential leader in the MASH treatment landscape, especially given the high mortality rates associated with MASH-related cirrhosis. The results also highlight the potential of longer treatment durations for improved outcomes.

Comparison to Industry Standards

• The results of the SYMMETRY study are notable when compared to other MASH treatments in development.
• While other companies like Madrigal with Resmetirom and 89Bio with Pegozafermin have shown improvements in fibrosis, Akero's EFX is the first to demonstrate statistically significant reversal of cirrhosis.
• Semaglutide, a GLP-1 agonist, has shown some efficacy in MASH, but EFX appears to have a more pronounced effect on cirrhosis reversal.
• Other compounds like Selonsertib, Obeticholic acid, and Simtuzumab have failed to show similar results in clinical trials.
• The 39% reversal rate in the primary analysis and 29% in the ITT analysis for EFX are significantly higher than the results reported for other treatments in similar patient populations.
• The sustained response observed from week 36 to week 96 with EFX is also a positive differentiator.

Stakeholder Impact

• Shareholders are likely to react positively to the strong clinical results and the potential for EFX to become a leading treatment for MASH.
• Patients with MASH-related cirrhosis may benefit from a new treatment option that has shown the potential to reverse their condition.
• Employees of Akero Therapeutics may be motivated by the positive results and the company's progress.
• The medical community may see this as a significant advancement in the treatment of MASH.

Next Steps

• The company will continue evaluating 50mg EFX in the Phase 3 SYNCHRONY Outcomes study.
• The company will continue to enroll patients in the Phase 3 SYNCHRONY Histology and Real-World studies.
• The company expects to report results for the SYNCHRONY Real-World study in the first half of 2026.
• The company expects to report results for the SYNCHRONY Histology study in the first half of 2027.

Key Dates

Keywords

efruxifermin, EFX, MASH, cirrhosis, liver disease, fibrosis, clinical trial, Phase 2b, SYMMETRY study, metabolic dysfunction-associated steatohepatitis