Alterity Therapeutics Announces Positive Interim Results from ATH434-202 Phase 2 Trial in MSA

Alterity Therapeutics, a biotechnology company focused on developing treatments for neurodegenerative diseases, has announced promising interim results from its ATH434-202 open-label Phase 2 clinical trial. This trial is investigating the effectiveness of ATH434 in patients with multiple system atrophy (MSA), a rapidly progressing neurodegenerative disorder.

The trial's interim analysis covered clinical and biomarker data from 7 participants treated with ATH434 for 6 months, along with neuroimaging data from 3 participants treated for 12 months. After 6 months, 43% of participants showed improvement in their daily living activities as measured by the Unified MSA Rating Scale Part I (UMSARS), which assesses daily living activities such as speech, swallowing, and walking. Furthermore, 29% of participants either stabilized or showed improvement in their neurological symptoms, as evaluated by both the treating physician and the patient.

The participants who demonstrated clinical improvement also exhibited reduced iron accumulation in the brain and stable levels of neurofilament light chain (NFL), a marker of neuronal injury, compared to those who declined. This suggests that ATH434 could potentially modify the disease course by stabilizing certain biomarkers associated with MSA.

Dr. David Stamler, CEO of Alterity, expressed optimism regarding these interim findings. He noted that MSA typically progresses rapidly and unrelentingly, making the positive outcomes observed in some patients quite significant. The stabilization of brain biomarkers among clinical responders further reinforced the potential efficacy of ATH434.

Dr. Daniel Classen of Vanderbilt University Medical Center, a principal investigator in the study, also highlighted the importance of these findings. He emphasized that the data support the chosen biomarkers and clinical endpoints, enhancing confidence in ATH434’s potential to affect MSA positively.

The interim results revealed that ATH434 was generally well-tolerated, with no severe adverse events reported. Most reported side effects were mild to moderate in severity.

The trial's primary aim is to assess the impact of 12 months of ATH434 treatment on brain volume and other biomarkers in a more advanced MSA patient group compared to those enrolled in Alterity's randomized Phase 2 trial. The final 12-month data from ATH434-202 are anticipated in the first half of 2025.

ATH434 is designed to inhibit the aggregation of pathological proteins involved in neurodegeneration. Preclinical studies have demonstrated that ATH434 can reduce α-synuclein pathology and preserve neuronal function by normalizing brain iron balance. This makes ATH434 a promising candidate not only for MSA but also for other Parkinsonian disorders, including Parkinson’s disease.

In addition to the ATH434-202 trial, a separate randomized, double-blind, placebo-controlled Phase 2 clinical trial (ATH434-201) is also underway, focusing on early-stage MSA patients. ATH434 has received Orphan Drug designation from both the U.S. FDA and the European Commission for the treatment of MSA.

Multiple System Atrophy is a debilitating neurological condition characterized by the degeneration of multiple brain regions. It affects autonomic functions such as blood pressure regulation and bladder control, and leads to impaired movement and coordination. The condition is marked by the accumulation of α-synuclein protein within glial cells and affects at least 15,000 individuals in the U.S. Currently, there are no treatments available to slow the disease progression, underscoring the importance of research efforts such as those involving ATH434.

Alterity Therapeutics, headquartered in Melbourne, Australia, and San Francisco, California, remains committed to addressing neurodegenerative diseases. Alongside ATH434, the company is also working on a broad drug discovery platform aimed at treating the underlying pathology of neurological diseases.