Alterity Reports Significant Phase 2 Efficacy for ATH434 in MSA Patients

Promising Phase 2 Results for a Rare Neurodegenerative Disease

Alterity Therapeutics has presented compelling data from its ATH434-201 Phase 2 clinical trial at the American Neurological Association Annual Meeting, highlighting the potential of its lead candidate, ATH434, to modify the course of Multiple System Atrophy (MSA). This rare and rapidly progressive neurodegenerative disorder currently lacks any approved therapies that can slow its progression, making these findings particularly significant.

The randomized, double-blind, placebo-controlled trial enrolled 77 adults with MSA, administering either 50 mg or 75 mg of ATH434 twice daily over 12 months. The study demonstrated that ATH434 treatment led to clinically meaningful improvements on the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I, which measures disability in daily living activities affected by MSA. These improvements were consistent across other assessments, including motor performance and patient-reported symptom scales.

Target Engagement and Safety Profile

Beyond clinical efficacy, biomarker analyses revealed that ATH434 effectively reduced iron accumulation in brain regions impacted by MSA, a key pathological hallmark of the disease. This target engagement supports the drug’s proposed mechanism as an iron chaperone that restores iron balance and inhibits pathological protein aggregation.

Importantly, ATH434 was well tolerated, with adverse event rates comparable to placebo and no serious adverse events attributed to the drug. This safety profile, combined with its efficacy signals, strengthens the case for ATH434 as a promising disease-modifying therapy.

Innovative Trial Design and Next Steps

The trial also incorporated wearable sensor technology to monitor motor activity in outpatient settings, providing a more comprehensive picture of patient function beyond the clinic. Data indicated increased activity levels among those treated with ATH434, suggesting maintained or improved mobility.

With Fast Track and Orphan Drug designations granted by the FDA, Alterity is well positioned to advance ATH434 through further clinical development. However, the company will need to address baseline differences in disease severity observed between dosing groups and confirm these findings in larger, longer-term studies.

As the neurodegenerative disease field eagerly watches, ATH434’s progress offers a glimmer of hope for patients facing the daunting challenges of MSA.