ATH434 Cuts MSA Disease Progression by Half in Phase 2 Open-Label Trial

Positive Signals in a Challenging Disease

Alterity Therapeutics has announced positive topline data from its ATH434-202 open-label Phase 2 clinical trial, evaluating its lead candidate ATH434 in patients with advanced Multiple System Atrophy (MSA). This rare and rapidly progressive neurodegenerative disorder currently has no approved disease-modifying treatments, making any clinical progress highly significant.

The trial enrolled 10 participants with more advanced MSA than those in Alterity’s previous double-blind Phase 2 study. Over 12 months, ATH434 treatment was associated with a roughly 50% reduction in disease progression as measured by the Modified Unified MSA Rating Scale Part I (UMSARS I), compared to historical controls. Notably, 30% of participants experienced stabilization or improvement in overall neurological symptoms, an unexpected outcome in this patient population.

Biomarker Evidence Supports Clinical Findings

Beyond clinical assessments, the trial incorporated neuroimaging and biochemical biomarkers to evaluate target engagement and disease impact. ATH434 slowed brain atrophy in regions typically affected by MSA, as measured by the MSA Atrophy Index, and reduced iron accumulation in key brain areas such as the putamen and globus pallidus. These findings mirror those seen in the earlier Phase 2 double-blind trial, reinforcing the drug’s potential mechanism of action as an iron chaperone that modulates pathological protein aggregation.

Importantly, the drug was well tolerated with no serious adverse events attributed to ATH434. Mild to moderate side effects were reported, and three participants discontinued the study, two due to disease progression and one for an unrelated adverse event. Stability in plasma and cerebrospinal fluid neurofilament light chain levels, a marker of neuronal injury, further suggests a neuroprotective effect.

Implications and Next Steps

Alterity’s CEO, Dr. David Stamler, emphasized the consistency of these results with prior data and the strong rationale to advance ATH434’s clinical development. With Fast Track and Orphan Drug designations from the U.S. FDA, ATH434 is positioned as a promising candidate to address an urgent unmet medical need. The company is expected to pursue larger, controlled Phase 3 trials to confirm efficacy and safety in a broader MSA population.

While the small sample size and open-label design limit definitive conclusions, these findings represent a meaningful step forward in a field where therapeutic options are scarce. The neurodegenerative disease community will be watching closely as Alterity progresses ATH434 toward potential regulatory approval and patient access.