Alterity Therapeutics Confirms Effectiveness of ATH434 Drug Against Advanced MSA

Alterity Therapeutics (ASX: ATH) has released positive topline data from an open label Phase 2 clinical trial of lead candidate ATH434 on 10 patients with advanced multiple system atrophy (MSA).

Data from the ATH434-202 trial showed the oral drug conferred a clinical benefit on areas of impairment in MSA and was able to stabilise key neurological biomarkers that underpin the pathology of the disease.

Pre-clinical studies have previously shown that ATH434 can reduce ⍺-synuclein pathology and preserve neuronal function by re-distributing iron in the central nervous system.

Reduced Progression

Over the ATH434-202 trial’s 12-month treatment period, disease progression in patients was reduced by approximately 50% (as assessed by the Modified Unified MSA Rating Scale Part I, or UMSARS I) when compared to historical controls.

In addition, 30% of patients reported a stabilising of neurological symptoms, an unexpected result in advanced MSA patients.

ATH434 also stabilised low blood pressure in the new trial, repeating a pattern observed in the ATH434-201 study.

Slowed Brain Atrophy

Neuro-imaging data indicated that ATH434 could slow brain atrophy in advanced patients when compared to placebo-treated participants in Alterity’s previous ATH434-201 study.

The effects on brain volume were also comparable to those of participants in the ATH434-201 trial’s 75-milligram dosage group.

In the ATH434-202 trial, the drug led to reduced iron accumulation compared to placebo-treated patients in ATH434-201, providing further evidence of target engagement.

Robust Efficacy

Alterity chief executive officer David Stamler said the latest results confirmed the robust efficacy observed in the ATH434-201 study.

“The clinical and biomarker outcomes from our Phase 2 studies have been consistent and strongly support advancing our ATH434 program in MSA,” he said.

“We believe that ATH434 has the potential to slow the progression of this devastating disease and we are committed to bringing this new therapy to patients as soon as possible.”

Rare Disease

MSA is a rare but rapidly-progressive neurodegenerative disease characterised by failure of the autonomic nervous system and impaired movement due to the progressive loss of function and death of different types of nerve cells in the brain and spinal cord, causing profound disability in patients.

A pathological hallmark of MSA is the accumulation of the protein ⍺-synuclein within the support cells of the central nervous system (known as glia) and neuron loss in multiple brain regions.

While some MSA symptoms can be treated with medications, there are currently no approved therapies that are able to slow or cure the disease.

Peer Research

Alterity has been featured in a peer-reviewed journal for an innovative neuroimaging measure developed in a Biomarkers of Progression in Multiple System Atrophy (bioMUSE) natural history study.

The publication — titled The MSA Atrophy Index (MSA-AI): An Imaging Marker for Diagnosis and Clinical Progression in Multiple System Atrophy — described how deep-learning methods were used to define the neuroanatomy of key regions in the brain and the development of a novel brain atrophy measure for tracking disease progression in MSA patients over 12 months.

The results were correlated with clinical measures of disease severity over the same timeframe.

Assessing Brain Volume

“This research used state-of-the-art technology employed in the bioMUSE study that goes above and beyond traditional MRI methods for assessing brain volume in patients with MSA,” Mr Stamler said.

“We observed that statistically-significant reductions in brain volume correlate with clinical worsening of the disease and we now have superior tools for diagnosing MSA and tracking brain atrophy over time.”

Mr Stamler said the results underscored the importance of utilising advanced neuroimaging methods and analytical tools in evaluating MSA.