Alterity presents positive ATH434 phase II data at key Parkinson’s conference

• Alterity presents positive phase II data for ATH434 at 2025 International Congress of Parkinson’s Disease and Movement Disorders
• Data demonstrates ATH434 slows disease progression and stabilises orthostatic hypotension
• New analysis increases overall confidence in the Phase 2 trial results –

Special Report: Alterity Therapeutics has presented positive phase II data at the 2025 International Congress of Parkinson’s Disease and Movement Disorders showing the potential of its lead drug candidate ATH434 to treat Multiple System Atrophy (MSA).

Alterity Therapeutics (ASX:ATH) CEO Dr David Stamler presented new analyses from the phase II double-blinded ATH434-201 trial in MSA, showing positive effects on slowing disease progression and stabilising orthostatic hypotension (OH).

One of the most challenging symptoms of MSA to manage, OH is a form of low blood pressure that occurs when a person goes from sitting to standing and causes dizziness, light-headedness or fainting.

The analysis included 71 patients randomised to ATH434 50 mg (n=25), 75 mg (n=24) or placebo (n=22), administered twice daily.

ATH434 demonstrated clinically meaningful improvements in disease severity on the modified UMSARS I scale, with a 48% relative treatment effect at 50 mg and a 30% effect at 75mg. When accounting for the baseline OH blood pressure change, the efficacy signal in the 75 mg dose group strengthened for a relative treatment effect of 35%.

Importantly, Alterity said ATH434 stabilised OH over 52 weeks, whereas placebo patients worsened.

Additional measures, including the Clinical Global Impression of Severity scale and wearable movement sensors, showed that ATH434 slowed disease progression improved daily activity and motor function compared to placebo.

Neuroimaging biomarkers indicated that ATH434 reduced iron accumulation in key brain regions and showed trends toward slowing brain atrophy.

The therapy was well tolerated, with similar adverse events to placebo and no serious events attributed to ATH434.

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About MSA and ATH434

MSA is a rare, neurodegenerative Parkinsonian disorder affecting up to 50,000 patients in the US, characterised by failure of the autonomic nervous system and impaired movement.

The symptoms reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord.

MSA is a rapidly progressive disease and causes profound disability and as it shares symptoms with Parkinson’s disease, diagnosis is often challenging.

The disease is driven by aggregation of a protein called alpha-synuclein and excess iron in the central nervous system (CNS).

ATH434 is a small molecule drug candidate which has been granted US Food and Drug Administration (FDA) fast track designation along with orphan drug designation (ODD) in the US and Europe for treatment of MSA.

ATH434 takes a novel approach to MSA by addressing pathologic protein aggregation by restoring iron balance, offering what could be the first disease-modifying therapy.

Improving diagnosis and tracking disease progression

In addition, data was presented assessing state-of-the-art neuroimaging and biomarkers employed in the phase II trial to refine diagnosis of MSA and track the evolution of the disease across the two main clinical phenotypes – parkinsonian (MSA-P) and cerebellar (MSA-C).

At the conference Alterity’s vice president of research and non-clinical development Dr Margaret Bradbury highlighted the relationship between α-synuclein protein aggregation, imaging biomarkers and disease severity in MSA.

In the Phase II trial, imaging biomarkers supported an MSA diagnosis in 96% of participants, compared with 79% based on α-synuclein in cerebrospinal fluid (CSF) alone.

Some participants whose CSF profiles suggested Parkinson’s still showed imaging consistent with MSA.

The presentation concluded that combining protein aggregation data with imaging and clinical assessments — a multimodal approach — may improve diagnostic accuracy and guide patient selection for future MSA trials.

Vanderbilt University Medical Center Department of Neurology research assistant professor Dr Paul Trujillo authored data assessing neuroimaging patterns in the phase II trial.

The trial compared clinical assessments with MRI and other imaging tests measuring brain iron and atrophy.

MRI results aligned with clinical classifications in 90% of cases, supporting its role as an objective biomarker, while in 10% of cases it revealed underlying changes not apparent clinically.

Together with the α-synuclein data, Trujillo’s assessment highlights the value of a multimodal approach combining biomarkers and imaging to improve diagnosis, track disease progression and inform patient selection in future MSA studies.

‘ATH434 has great potential’

Stamler said the aggregate data from Alterity’s phase II trial continued to demonstrate the potential of ATH434 as a disease modifying therapy for MSA.

“The positive data from our ATH434-201 trial have demonstrated a slowing of disease progression and stabilisation of orthostatic hypotension, one of the most challenging MSA symptoms to manage.”

Stamler said the data strengthened confidence in ATH434 as a potential disease-modifying treatment for MSA, targeting activities of daily living and orthostatic hypotension.

“When we accounted for baseline differences in an important predictor of disease progression, the efficacy signal at the 75 mg dose strengthened meaningfully on the key clinical endpoint at 52 weeks,” he said.

“This new analysis continues to support our belief that ATH434 has great potential to treat this devastating disease.

“We remain committed to advancing ATH434 to the next stage of development while striving to become the market leader dedicated to improving the overall treatment paradigm for MSA.”

This article was developed in collaboration with Alterity Therapeutics, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.