Alterity Therapeutics Ltd (ASX:ATH) has received official US Food and Drug Administration meeting minutes confirming a registrational pathway for ATH434, its lead drug candidate for Multiple System Atrophy (MSA).
The FDA minutes confirm the previously announced End-of-Phase 2 meeting outcomes and provide further detail on the planned Phase 3 protocol. Importantly, the regulator agreed that a single pivotal Phase 3 trial, supported by confirmatory evidence, could support approval of ATH434 for the treatment of MSA.
Pivotal Phase 3 trial activities remain on track to begin by the end of 2026.
FDA alignment sharpens registration strategy
The official minutes confirm the key elements of Alterity’s proposed Phase 3 program and the path toward a potential New Drug Application filing.
Chief executive officer David Stamler said the minutes confirmed the alignment reached with the FDA and provided a well-defined clinical development strategy for registration.
“The FDA’s willingness to accept a single pivotal trial supported by confirmatory evidence reflects a clear pathway for ATH434 in MSA,” he said. “With the Phase 3 design elements confirmed, we are finalizing the protocol and remain on track to initiate Phase 3 trial activities by year-end 2026.”
Phase 3 trial design confirmed
The FDA agreed with the proposed Phase 3 trial design, including the study population, treatment regimen and efficacy endpoints.
The primary endpoint will be the 11-item UMSARS Part I rating scale, a functional measure of activities of daily living affected in MSA. Key secondary endpoints include the Swallowing Disturbance Questionnaire, Orthostatic Hypotension Symptom Assessment and Clinical Global Impression of Severity.
The trial is expected to enrol about 200 patients, who will be randomised on a 1:1 basis to receive either ATH434 50 mg or matching placebo twice daily for 12 months.
Confirmatory evidence to support single pivotal study
Alterity expects data from its ATH434-201 Phase 2 clinical trial to provide the confirmatory evidence required to support the single pivotal trial approach.
The FDA also indicated that the anticipated size of the safety database at the conclusion of Phase 3 was reasonable. Alterity plans to offer an open-label extension to participants who complete the Phase 3 trial, allowing continued treatment and further strengthening of the ATH434 safety database.
ATH434 targets rare neurodegenerative disease
ATH434 is an oral agent designed to reduce iron accumulation and inhibit abnormal protein aggregation associated with neurodegeneration.
The candidate has shown potential to reduce alpha-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain in preclinical models. It has also delivered positive results in Phase 2 trials in MSA, including evidence of clinical efficacy, target engagement through biomarkers and a favourable safety profile.
MSA is a rare and rapidly progressive neurodegenerative disease that causes profound disability. It affects up to 50,000 people in the US and currently has no approved treatment that slows disease progression.
About Alterity Therapeutics
Alterity Therapeutics is a clinical-stage biotechnology company developing disease-modifying therapies for neurodegenerative diseases, with a focus on MSA and related Parkinsonian disorders.
The company is preparing to initiate a pivotal Phase 3 trial in MSA and is also advancing a broader drug discovery platform aimed at generating patentable compounds targeting the underlying pathology of neurological diseases. Alterity is based in Melbourne, Australia, and San Francisco, California.