Akero Therapeutics Releases Promising Results from Phase 2b HARMONY Trial
Akero Therapeutics (Nasdaq: AKRO) has revealed the 96-week outcomes from its Phase 2b HARMONY trial, which assessed the efficacy of efruxifermin (EFX) in patients diagnosed with pre-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH). The findings published in The Lancet highlight significant therapeutic benefits, with 49% of participants receiving a 50mg dose of EFX experiencing at least one stage of fibrosis improvement, in contrast to only 19% in the placebo group. Notable results also indicated that 40% and 37% of patients in the 28mg and 50mg groups, respectively, achieved MASH resolution, compared to just 19% for the placebo cohort. Furthermore, the composite endpoint of both MASH resolution and fibrosis improvement was met by 35% of the 50mg group and 28% of the 28mg group.
Study Findings and Patient Responses
The trial’s results are particularly encouraging, as they show that 92% of the patients who responded positively at week 24 sustained their improvement by week 96. EFX was generally well received by participants, with mostly mild to moderate gastrointestinal side effects reported. These outcomes bolster the argument for EFX’s role in mitigating disease progression among individuals with MASH.
Key Insights from the HARMONY Trial
The HARMONY trial’s 96-week results illustrate EFX’s impressive ability to improve fibrosis in patients with pre-cirrhotic MASH, suggesting a possible reversal of the disease in nearly one-third of those on the higher dosage. The data indicates a significant advancement in treatment options for MASH, as 49% of participants in the 50mg group achieved fibrosis improvement without worsening MASH, compared to 19% for placebo (p=0.0030). This is crucial because improvements in fibrosis are closely linked to better clinical outcomes in MASH patients.
The durability of the treatment response is particularly noteworthy—92% of patients who responded at week 24 continued to show positive results at week 96. Additionally, 63% of those who initially did not respond became responders with ongoing treatment. This suggests that EFX might offer cumulative benefits over time, unlike many therapies that tend to plateau.
The composite endpoint results are compelling, with 35% of participants receiving the 50mg dose achieving both MASH resolution and fibrosis improvement compared to just 7% for the placebo group (p=0.0013). This level of efficacy approaches disease reversal, marking a significant achievement in treating a condition that has historically resisted pharmacological interventions.
Safety Profile and Ongoing Research
The improvements in metabolic health, including decreased dyslipidemia and enhanced insulin sensitivity, highlight EFX’s mechanism as an FGF21 analogue that addresses the systemic dysfunction associated with MASH. While the safety profile remains consistent and mostly involves mild gastrointestinal events, the observed decrease in bone mineral density after 96 weeks of treatment necessitates careful monitoring in future studies.
These findings, alongside previously reported efficacy for EFX in patients with MASH cirrhosis from the SYMMETRY trial, position EFX as a potentially groundbreaking treatment capable of addressing the entire spectrum of MASH severity, especially for patients with advanced fibrosis at higher risk for liver complications.
Future Directions for Efruxifermin
Continuing research is vital, as the current Phase 3 SYNCHRONY clinical trial program seeks to further confirm EFX’s therapeutic potential. Efruxifermin is Akero’s leading candidate for MASH and is currently being explored in three ongoing Phase 3 studies. Previous Phase 2 trials have shown EFX’s ability to reverse fibrosis, resolve MASH, and enhance overall metabolic health, underscoring its promise for tackling this complex disease.
Understanding MASH and Its Implications
Metabolic dysfunction-associated steatohepatitis (MASH) is a serious condition impacting approximately 17 million Americans. Characterized by excessive fat accumulation in the liver, MASH can lead to inflammation and fibrosis, potentially progressing to cirrhosis, liver failure, or cancer. With around 20% of MASH patients facing a progression to cirrhosis—an outcome with a significantly higher mortality risk—there are currently no approved treatments available for this condition. MASH represents the fastest-growing cause of liver transplants and liver cancer in both the U.S. and Europe, highlighting the urgent need for effective therapies.
About the HARMONY Trial
The HARMONY trial was a Phase 2b multicenter, randomized, double-blind, placebo-controlled study involving adult participants with biopsy-confirmed MASH and fibrosis stages 2 or 3. A total of 128 patients were enrolled and randomized to receive once-weekly subcutaneous doses of either 28mg, 50mg EFX, or a placebo for 96 weeks. The primary efficacy endpoint focused on the proportion of participants achieving at least one stage of fibrosis improvement without worsening MASH, while secondary endpoints evaluated MASH resolution, liver fibrosis improvements, and various health metrics.
About Akero Therapeutics
Akero Therapeutics is dedicated to developing innovative treatments for patients suffering from serious metabolic diseases that currently lack effective therapies, including MASH. With efruxifermin as its lead candidate, Akero is advancing its research through three ongoing Phase 3 clinical studies aimed at confirming the promising results seen in prior trials. The company is headquartered in South San Francisco, focusing on addressing the multifaceted nature of MASH and its associated health risks.
Forward-Looking Statements
This announcement contains forward-looking statements, which are inherently subject to risks and uncertainties that may cause actual outcomes to differ significantly from those anticipated. These statements include projections related to Akero’s clinical development plans, therapeutic potential of EFX, and operational capabilities. The company does not undertake any obligation to update these forward-looking statements based on new information or developments.
