Iron Chaperone Granted Fast Track Status for Multiple System Atrophy

The Food and Drug Administration (FDA) has granted Fast Track designation to ATH434 for the treatment of multiple system atrophy (MSA).

MSA is a progressive neurodegenerative disorder characterized by slowed movement and/or rigidity, autonomic instability, and impaired balance and/or coordination. Administered orally, ATH434 is designed to reduce α-synuclein aggregation and oxidative stress by binding to and redistributing excess loosely bound iron in the brain. This approach is expected to limit neurodegeneration in patients with MSA.

The Fast Track designation is supported by data from the double-blind, placebo-controlled, phase 2 ATH434-201 trial (ClinicalTrials.gov Identifier: NCT05109091), which evaluated the safety and efficacy of ATH434 in 77 adults with early stage MSA. Study participants were randomly assigned to receive 1 of 2 dose levels of ATH434 (50mg or 75mg) or placebo orally twice daily. The primary endpoint was the change in iron content as measured by brain magnetic resonance imaging (MRI) from baseline to week 52.  

The modified intent-to-treat (mITT) population included patients who received study drug and had at least 1 MRI evaluation for brain iron at 6 months; there were approximately 20 patients per arm in the mITT. Findings showed treatment with ATH434 reduced or stabilized iron content in key brain regions affected by MSA. 

A key secondary endpoint was the change in Unified MSA Rating Scale (UMSARS) score. Compared with placebo, ATH434 demonstrated a 48% and 29% slowing of clinical progression at the 50mg (P =.03) and 75mg (P =.2) doses, respectively, at week 52. For the 75mg dose group, a 62% slowing of progression was observed at week 26 (P =.05).

Clinical benefits with ATH434 were also observed based on improvements in Clinical Global Impression of Severity scale scores, Parkinson Plus total motor scale scores, and Orthostatic Hypotension Symptom assessment scores. Increased activity (eg, step count, bouts of walking, total walking time, standing time) based on wearable sensor data was also noted in the treatment groups.

Regarding safety, ATH434 was found to be well tolerated. No serious adverse events were reported with treatment.

“Receiving the FDA’s Fast Track designation for ATH434, alongside the Orphan Drug designation we have already received, underscores the promise of this novel agent to address the urgent need for a disease modifying therapy for individuals with MSA,” said, David Stamler, MD, Chief Executive Officer of Alterity. “This designation reinforces the potential of ATH434 as demonstrated by recent scientific findings related to its mechanism of action and the robust and clinically meaningful efficacy from our double-blind phase 2 clinical trial.”

This article originally appeared on MPR