Potential Promise Behind ATH434 for Multiple System Atrophy: Daniel Claassen, MD, MS

WATCH TIME: 3 minutes

"A lot of times patients come in with a Parkinson's disease diagnosis, they may have a couple red flags that make you think, 'Oh, this isn't like a run-of-the-mill patient with Parkinson, and that might or might not be MSA... What we really are trying to do is come up with biofluid and neuroimaging biomarkers that help us get a better sense if this patient really has what we think is an MSA diagnosis."

Multiple system atrophy (MSA), a rare, neurodegenerative disorder characterized by failure of the autonomic nervous system and impaired movement, has no approved therapeutics currently. Despite this, through recent research there has been a growing understanding of pathophysiology of the disease, with several industry leaders starting to take interest. One therapy, Alterity’s ATH434, continued to show promising results in a phase 2 study (NCT05864365) recently presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders, held September 27 to October 1, in Philadelphia, Pennsylvania.

One of 2 studies ran by Alterity, the phase 2 “202” study is a double-blind, placebo-controlled study of patients with early MSA that tests 2 doses (50 mg, 75 mg) of ATH434 over a 12-month period. The study (n = 77) used change in Unified MSA Rating Scale (UMSARS), an assessment of MSA activities of daily living, as the primary outcome. According to Daniel Claassen, MD, MS, a study investigator, there was no worsening on motor severity that was out of proportion from natural history data, there were no other notable signals in terms of adverse events (AEs) or blood biomarkers that would be concerning of changes. Above all, the drug appeared safe and well tolerated, with future plans for continued development.

At MDS 2024, Claassen, director of the Huntington’s Disease Clinic at Vanderbilt University Medical Center, sat down to discuss the mechanism of action behind ATH434, citing how it focuses on reducing labile iron to prevent interaction with synuclein, which can lead to harmful protein aggregation. He also spoke about the challenges of early diagnosis in MSA, and how the definition of “early” MSA remains somewhat fluid. Furthermore, he provided clinical insight on the use of biomarkers, such as neurofilament light, in MSA diagnosis and trials. Claassen, an expert in neurodegenerative disorders, described how these markers, particularly related to iron accumulation in specific brain regions, help improve accuracy of diagnosing MSA and selecting appropriate patients for clinical trials.

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REFERENCE
1. Stamler D, Wong C, Trujilo P, Bradbury M, Lucas C, Claassen D. A Phase 2 Study of ATH434 a Novel Inhibitor of α-Synuclein Aggregation for the Treatment of Multiple System Atrophy. Presented at: Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 4