April 29, 2025 marked a milestone in neurodegenerative disease research, as Alterity Therapeutics presented new Phase 2 data for ATH434, their lead drug targeting Multiple System Atrophy (MSA). This rare, fast-progressing condition currently lacks any approved therapies that can slow or halt its relentless impact on movement, balance, and the autonomic nervous system.

ATH434 is designed to inhibit the abnormal build-up of alpha-synuclein protein aggregates, believed to be central in the disease process, while also redistributing iron in the central nervous system. To test its effects, Alterity conducted both a double-blind, placebo-controlled trial in early-stage MSA and an open-label extension for individuals with more advanced disease.

Data from these trials are compelling. In the earlier phase, patients who received ATH434 experienced clinically and statistically significant slowing of disease progression as measured by the Modified Unified MSA Rating Scale Part I (UMSARS I) a key tool for evaluating decline in daily function. At the 50 mg dose, the risk of disease progression was slowed by nearly half compared to placebo over 12 months, while the 75 mg dose demonstrated substantial benefit both at the six and twelve month marks. Many patients also showed improvements in motor performance and a reduction in severity based on global measures of neurological function.

The more recent open-label extension, focusing on patients with later-stage disease, confirmed these results in a real-world setting. Over a 12-month period, disease progression on UMSARS I was reduced by approximately 50% compared to what has been observed historically in untreated patients. Importantly, nearly a third of participants in this advanced group saw their symptoms remain stable—a striking outcome given the relentless decline typically seen with MSA. Critical symptoms like orthostatic hypotension, which can cause sudden drops in blood pressure and falls, were stabilized in a majority of participants. The drug was well tolerated, with no serious adverse events attributed to treatment.

Neuroimaging results mirrored these clinical findings. Patients on ATH434 showed slower rates of brain atrophy, particularly in regions most affected by MSA, when compared to placebo groups and to typical patterns in specialized MRI measures. The effects on brain volume were comparable in the 75 mg groups across both studies, and levels of iron accumulation in vulnerable brain regions were significantly reduced, reinforcing that the drug was actively targeting the underlying disease biology.

Taken together, these results not only support the continued development of ATH434, but provide the first robust evidence that MSA progression can be meaningfully slowed in both early and more advanced stages. Researchers note that stabilizing symptoms in late-stage MSA is unprecedented, and families now have tangible hope for therapies that go beyond managing symptoms to altering the disease course itself.

With this strong Phase 2 data, Alterity is preparing for pivotal, global Phase 3 studies and emphasizes a renewed commitment to making ATH434 accessible to MSA patients worldwide. The company’s focus now turns to securing regulatory support and launching larger trials designed to confirm and expand upon these encouraging findings, with the ultimate goal of transforming the outlook for individuals living with this devastating neurological disorder.