Alterity Therapeutics’ ATH434 trial results suggest improved outcomes for MSA Patients

Alterity Therapeutics (ASX: ATH) has released positive interim data from an open-label Phase 2 clinical trial of its lead asset ATH434, showing stable or improved neurological symptoms in patients with multiple system atrophy (MSA).

The analysis of a total of ten participants included clinical and biomarker data on seven who were treated with daily oral doses of ATH434 for six months, as well as neuro-imaging data on three others who were treated with the same dose for 12 months.

In general, ATH434 was found to be well-tolerated by trial participants and most adverse events were considered mild to moderate in severity.

Improved symptoms

After six months of treatment, 43% of participants showed improvement on the Unified Multiple System Atrophy Rating Scale, indicating reduced disability in daily living activities.

Over the same period, 29% of participants had stable or improved neurological symptoms as assessed by the treating physician and the patient.

Importantly, clinical responders on average reported a reduced accumulation of iron on magnetic resonance imaging, as well as stable levels of neurofilament light chain (a marker of axonal injury), when compared to participants who declined.

Favourable outcomes

Alterity chief executive officer David Stamler said the interim results had been encouraging.

“As MSA is a rapidly progressive and unremitting disease, we expected to see a decline in all participants,” he said.

“Instead, we saw favourable clinical and biomarker outcomes in some patients, suggesting that ATH434 has the potential to modify the course of this devastating condition.”

“We were also very pleased to see that the clinical responders had biomarker evidence of stable disease as this provides an objective indication of potential efficacy.”

Earlier-stage patients

Mr Stamler said participants who stabilised or improved with ATH434 treatment had less advanced disease than those who progressed.

“This is noteworthy as we have enrolled earlier-stage MSA patients in our parallel ATH434-201 randomised, double-blind clinical trial,” he said.

“Although the number of patients studied so far is small, the new data reinforces that we have taken the right approach and increases my overall confidence in the ATH434 development program.”

Oral agent

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

The candidate has been shown pre-clinically to reduce α-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain.

As an iron chaperone, it is believed to have strong potential to treat Parkinson’s disease as well as various parkinsonian disorders such as MSA.

Orphan drug designation

Alterity’s Phase 1 studies demonstrated that ATH434 is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA.

It is currently being studied in the ATH434-201 Phase 2 clinical trial in patients with early-stage MSA and an ATH434-202 Phase 2 biomarker trial in patients with more advanced MSA.

ATH434 has been granted orphan drug designation for the treatment of MSA by the US Food and Drug Administration and the European Commission.

Rare disease

MSA is a rare, neurodegenerative disease characterised by failure of the autonomic nervous system.

Symptoms include slowed movement and/or rigidity, autonomic instability affecting involuntary functions such as blood pressure maintenance and bladder control and impaired balance and/or coordination, which increases a patient’s fall risk.

The symptoms are believed to reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord, eventually causing profound disability.

MSA affects at least 15,000 individuals in the US and there are currently no drugs available to slow disease progression or provide a cure.