- 01FDA aligns on ATH434 Phase 3 design; approval not assured.
- 02~200 patients, 50mg twice daily vs placebo for 12 months.
- 03Phase 2: ~52% less decline at week 52.
Alterity Therapeutics (ASX: ATH) has secured US Food and Drug Administration agreement on the design of its proposed pivotal Phase 3 trial of ATH434 for multiple system atrophy (MSA).
While approval is not guaranteed, the regulator has indicated that one pivotal trial supported by confirmatory evidence could provide the data needed for a potential new drug application.
The biotechnology developer has begun operational preparations for a study expected to enrol approximately 200 patients receiving ATH434 or placebo over 12 months.
The FDA endorsed the proposed study population, treatment regimen, and primary endpoint, the 11-item Unified Multiple System Atrophy Rating Scale Part I, which measures daily functioning.
Trial Design Taking Shape
Patients are expected to be randomised equally between a 50-milligram ATH434 dose and matching placebo, administered twice daily throughout the trial.
Alterity anticipates that its completed ATH434-201 Phase 2 study will provide the confirmatory evidence contemplated in the FDA feedback, but the proposed approach remains subject to clinical results and regulatory review.
The company has started finalising the protocol, selecting vendors and qualifying clinical sites, while the first registration batch of ATH434 has been manufactured.
“With the final minutes from our end-of-Phase 2 meeting, we have confirmed alignment with the FDA on the registrational pathway for ATH434 in MSA,” chief executive officer David Stamler said.
“That clarity has allowed us to begin the operational start-up activities as we prepare to initiate our Phase 3 trial.”
Phase 2 Clinical Evidence
Additional Phase 2 analyses presented in October showed approximately 52% slower functional decline at week 52 for patients receiving ATH434 50mg compared with placebo, using statistical methods planned for Phase 3.
The analysis also identified baseline cerebrospinal fluid neurofilament light chain measurements as predictors of functional decline, supporting their proposed inclusion in the next trial’s statistical assessment.
A peer-reviewed study from Alterity’s bioMUSE natural history program linked phosphorylated alpha-synuclein deposits in skin samples with blood-pressure changes on standing and later autonomic symptom scores in early MSA.
In August, Alterity received a US patent covering the crystalline mesylate salt form of ATH434 used in Phase 2 and intended for Phase 3, with protection extending to 2045.
The intellectual property supports potential future development in Parkinson’s disease, while any further therapeutic applications would require their own supporting development evidence.
Next Development Stage
The September-quarter cash balance included an approximately $3.98m Australian research and development tax refund, including interest, and about $5.5m in net option-related fundraising.
Under an underwriting arrangement, holders exercised 3,191,983 listed options before expiry and 8.4 million shortfall shares were issued, with proceeds earmarked for ATH434 development and working capital.
Net operating cash outflows were $1.34m for the quarter, leaving Alterity with 30.8 quarters of funding at that historical cash-use rate under its statutory calculation.
Alterity is evaluating strategic funding and partnering alternatives, including discussions with pharmaceutical companies, to support the planned late-stage development program.
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