Breakthrough in MASH Treatment: Akero’s Efruxifermin Shines in Phase 2b HARMONY Trial Analyses at EASL Congress 2025

The liver disease landscape is on the brink of a paradigm shift, thanks to new data from Akero Therapeutics’ Phase 2b HARMONY trial and its collaboration with HistoIndex. Presented at the EASL International Liver Congress 2025, the findings highlight the potential of efruxifermin (EFX) to reverse fibrosis in metabolic dysfunction-associated steatohepatitis (MASH) and underscore the transformative role of AI-driven digital pathology in accelerating drug development. For investors, this marks a critical inflection point for Akero, positioning it as a leader in a rapidly growing market.

The Science Behind the Breakthrough: EFX and AI-Driven Pathology

The HARMONY trial evaluated EFX, a once-weekly FGF21 analog, in 128 patients with pre-cirrhotic MASH (F2-F3 fibrosis). The study’s most striking revelation was the superior sensitivity of HistoIndex’s AI-based qFibrosis® over traditional pathology scoring. By quantifying collagen in liver biopsies, qFibrosis® identified fibrosis improvement in 18 out of 26 EFX 50mg patients at Week 24, compared to just 10 detected by conventional scoring. This “signal amplification” suggests that AI tools can detect treatment effects earlier, potentially shortening trial timelines and reducing the “noise” of biopsy variability.

By Week 96, 81% of EFX 50mg patients achieved fibrosis improvement via qFibrosis®, aligning with results from non-invasive tests like the ELF score and FibroScan. Crucially, over 50% of EFX-treated patients met all three endpoints, versus fewer than 5% on placebo, reinforcing EFX’s anti-fibrotic efficacy.

Clinical Implications: A New Standard for MASH Trials

The HARMONY data, combined with earlier results from Akero’s SYMMETRY trial (which showed fibrosis reversal in compensated cirrhosis, F4), positions EFX as the first therapy to address all stages of MASH. This is critical in a disease projected to affect 3 million Americans by 2030, driven by rising obesity and metabolic syndrome.

The use of qFibrosis® and non-invasive markers also sets a new standard for trial design. As Prof. Quentin Anstee noted in his oral presentation, this “roadmap” reduces reliance on subjective biopsy scoring, enabling faster, more accurate efficacy assessments. For investors, this could mean shorter development timelines and lower costs for future trials—a competitive edge in the crowded NASH/MASH space.

Market Opportunity and Investment Case

Akero’s pipeline is now advancing into pivotal Phase 3 trials under the SYNCHRONY program, targeting three cohorts: F2-F3 MASH (Histology), compensated cirrhosis (Outcomes), and real-world populations (MASLD). With no approved therapies for MASH, the market potential is enormous. Analysts estimate the global NASH drug market could reach $20–$35 billion by 2030, and Akero’s lead in fibrosis reversal could secure a dominant share.

The safety profile of EFX—mild gastrointestinal side effects with no serious treatment-related events—also reduces regulatory risks. Additionally, subgroup analyses showed consistent efficacy in patients with type 2 diabetes or using GLP-1 agonists, broadening its applicability in a population where comorbidities are common.

Conclusion: A Transformative Asset for a Growing Epidemic

The HARMONY trial data cements EFX’s status as a breakthrough therapy for MASH. With AI pathology enabling earlier, more precise efficacy signals and Phase 3 trials on track, Akero is poised to capitalize on a $35 billion market. The 77–81% fibrosis improvement rates in pre-cirrhotic patients, alongside non-invasive marker concordance, provide robust evidence of EFX’s clinical value.

For investors, the combination of strong clinical data, a streamlined development path, and a first-in-class positioning makes Akero a compelling play in a high-growth therapeutic area. As the NASDAQ Biotechnology Index (IBB) tracks the broader sector’s performance, Akero’s stock could see significant upside if the SYNCHRONY trials replicate these results. In a space where efficacy and commercialization timelines are make-or-break, Akero’s HARMONY data suggests it’s already ahead of the curve.

This article is for informational purposes only and does not constitute financial advice.