Alterity Therapeutics' ATH434 Shows Promise in Multiple System Atrophy Trials
Key Insights
Alterity Therapeutics (search) anticipates topline data from the ATH434-201 Phase 2 trial in early-stage Multiple System Atrophy (search) (MSA) by early February 2025.
Interim data from the ATH434-202 Phase 2 trial in advanced MSA suggests potential disease-modifying effects, with 30% of participants showing stable or improved clinical outcomes.
Non-clinical data highlights ATH434's neuroprotective qualities and mechanism of action, emphasizing the importance of iron-targeting agents in treating neurodegenerative diseases.
Alterity Therapeutics (search) is on track to release topline data from its ATH434-201 Phase 2 clinical trial in early-stage Multiple System Atrophy (search) (MSA) by early February 2025. The completion of the ATH434-201 study, a 12-month, double-blind trial, marks a significant milestone in the development of a potential disease-modifying treatment for this rare neurodegenerative condition.
The company's lead asset, ATH434, is being evaluated for its potential to treat various Parkinsonian disorders. David Stamler, M.D., Chief Executive Officer of Alterity, noted the "tremendous potential of our lead asset, ATH434, as a promising therapy to treat a variety of neurodegenerative diseases."
Positive Interim Results from ATH434-202 Trial
Interim data from the ATH434-202 Phase 2 trial in advanced MSA, presented at the International Congress of Parkinson's Disease (search) and Movement Disorders (MDS), showed promising results. Daniel O. Claassen, M.D., M.S., Professor of Neurology, Vanderbilt University Medical Center, presented data indicating that 30% of participants experienced stable or improved clinical outcomes, suggesting a potential disease-modifying effect.
Disease progression over 6 months was slower in treated patients compared to a historical group of untreated MSA patients, as measured by the Unified MSA Rating Scale (UMSARS) Part I. Clinical responders also exhibited stable brain iron and brain volume after 12 months of treatment. The stabilization of iron content in MSA-affected brain regions, along with stable levels of neurofilament light chain (NfL), suggests that ATH434 may slow neurodegeneration by modulating brain iron levels and reducing oxidative injury.
The topline 12-month results from the 202 trial are expected in the first half of calendar year 2025.
bioMUSE Natural History Study
Alterity's "Biomarkers of progression in Multiple System Atrophy (search)" (bioMUSE) natural history study has yielded promising data for tracking MSA progression and characterizing the disease using various biomarkers. Data presented at the 35th International Symposium on the Autonomic Nervous System highlighted the use of advanced MRI technology to track changes in brain volume in specific regions affected by MSA. Paula Trujillo Diaz, PhD, Research Assistant Professor, Department of Neurology, Vanderbilt University Medical Center, presented findings showing that significant reductions in brain volume over 12 months correlated with clinical worsening of the disease.
Novel Mechanism of Action for ATH434
A peer-reviewed publication in Metallomics described the importance of iron and iron-targeting agents like ATH434 in treating neurodegenerative diseases. The publication, led by Ashley Pall, Department of Pharmaceutical Sciences at Wayne State University, demonstrated how ATH434 targets the labile, or reactive, form of iron, which can be damaging to cells in excess. The iron-binding properties of ATH434 support its characterization as an iron chaperone, targeting the toxic form of iron involved in the pathogenesis of Friedreich's Ataxia (search), Parkinson's disease (search), and MSA.
Neuroprotective Effects of ATH434
New data presented at the Society for Neuroscience 2024 further elucidated ATH434's potential as a disease-modifying treatment for neurodegenerative diseases. The presentation demonstrated that ATH434's neuroprotective and mitochondrial protectant properties include reducing lipid damage in neuronal injury models. Dr. Daniel J. Kosman, Distinguished Professor of Biochemistry at the State University of New York at Buffalo, directed the study, which distinguished ATH434's antioxidant properties from those of other iron-binding agents used for treating iron overload.
ATH434 for Parkinson's Disease
Data presented at MDS also indicated that ATH434 treatment led to lower iron levels in the substantia nigra and improved motor performance in monkeys with experimentally induced Parkinson's disease (search). At week 12, all ATH434-treated macaques had stable or improving scores from Baseline, while two of three vehicle-treated macaques did not demonstrate improvement. These favorable outcomes were associated with increased levels of striatal synaptophysin, suggesting functional recovery of nerve endings in this critical motor pathway.