Alterity Therapeutics shows positive ATH434 Phase 2 trial results for Multiple System Atrophy

Alterity Therapeutics (ASX: ATH) has announced positive topline results from a Phase 2 clinical trial of lead candidate ATH434-201 on patients with early-stage multiple system atrophy (MSA).

ATH434 is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration.

MSA is a rare neurodegenerative disease characterised by failure of the autonomic nervous system and impaired movement, with symptoms reflecting the progressive loss of function and death of different types of nerve cells in the brain and spinal cord.

Meaningful benefit

The randomised, double-blind, placebo-controlled trial produced a clinically meaningful benefit at both 50-milligram and 75mg doses.

It also generated a 48% improvement on the modified UMSARS Part I, a functional rating scale that assesses disability in daily living activities in MSA patients.

Trends of improved motor performance were observed on the Parkinson’s Plus rating scale and overall benefit was shown on the Clinical Global Impression of Severity at the 50mg dose.

Iron accumulation

Biomarkers used to evaluate potential drug effect and target engagement showed that the 50mg dose reduced the accumulation of iron in multiple MSA-affected brain regions, while the 75mg dose did so only in the globus pallidus.

The reduced accumulation was significant for the 50mg dose group at 26 weeks and approached statistical significance at 52 weeks.

Trends in the preservation of brain volume were observed in the 50mg and 75mg groups relative to placebo at 26 weeks and 52 weeks of treatment.

Slowed progression

Alterity chief executive officer Dr David Stamler said the trial had shown that ATH434 could significantly slow the clinical progression of the rare and rapidly progressive disease.

“Currently, there are no approved treatments to slow the progression of MSA,” he said,  “however, these results show that ATH434’s targeted iron engagement may truly have a disease-modifying effect.”

“The fact that we achieved statistical significance on the UMSARS scale is extremely meaningful because it assesses the functional areas affected by MSA and is the endpoint needed to support approval by the US Food and Drug Administration (FDA).”

Neurodegenerative disease

MSA is a rapidly progressive condition affecting at least 15,000 individuals in the US that ultimately causes profound disability in patients.

A pathological hallmark of MSA is the accumulation of the protein α-synuclein within the support cells of the central nervous system and neuron loss in multiple brain regions.

Based on the strength of the Phase 2 data, Mr Stamler said Alterity would commence engagement with the FDA to discuss a path forward for accelerating ATH434’s development.