Alterity Therapeutics (ASX:ATH) has announced that the US Food and Drug Administration has agreed on the key design elements for a pivotal Phase 3 trial of ATH434 in Multiple System Atrophy following a successful End of Phase 2 meeting.
The company said the agency accepted its proposed study population, the 11-item UMSARS Part I as the primary endpoint, and the 50 mg twice-daily dose that produced clinically and statistically significant benefit in Phase 2, in which ATH434 slowed disease progression by 48 per cent versus placebo.
The Phase 3 study is planned as a randomised, double-blind, placebo-controlled trial of about 200 participants, treated for 12 months, and will include key secondary measures such as the Swallowing Disturbance Questionnaire, the Orthostatic Hypotension Symptom Assessment, and the Clinical Global Impression of Severity.
The FDA also agreed with the statistical approach and indicated the anticipated safety database at the end of Phase 3 would be reasonable. Alterity says trial activities remain on track to begin by year-end 2026.
ATH434 previously received Fast Track and Orphan Drug designations from the FDA and showed robust signals in a 77-participant Phase 2 study that tested 50 mg and 75 mg twice daily. That Phase 2 trial found improvement on the modified UMSARS Part I, along with supportive findings on global impression scales, patient-reported swallowing and orthostatic symptom measures, wearable sensor activity, and biomarker evidence of target engagement and reduced iron accumulation in affected brain regions. ATH434 was well tolerated with adverse event rates similar to placebo.
David Stamler M.D. chief executive officer of Alterity, said, "Achieving alignment with FDA at the End of Phase 2 meeting is a critical step for our Phase 3 program in MSA providing the clarity we need to advance to this next stage We are encouraged by the FDA's agreement with us on the key elements of our Phase 3 program namely the study population efficacy endpoints treatment regimen and anticipated safety database providing a well defined registrational pathway built on the strength of our Phase 2 data The successful outcome of the meeting is an important de risking milestone and gives us confidence as we finalize the protocol and prepare to initiate trial activities by year end 2026 The favorable outcome of the meeting is a testimony to the depth of experience our team brings to collaborating with the FDA especially on neurology development programs I am confident that ATH434 is well positioned to become a disease modifying therapy for individuals living with MSA."
Multiple System Atrophy is a rare, rapidly progressive neurodegenerative disease with no approved therapy that affects autonomic function, movement, and balance and is characterised pathologically by abnormal α-synuclein accumulation. Alterity said ATH434 is an oral iron chaperone intended to redistribute excess iron and inhibit abnormal protein aggregation with the potential to address Parkinsonian disorders as well as MSA.