Alterity Therapeutics (ASX:ATH) has announced positive topline results from the ATH434-201 randomised, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage multiple system atrophy (MSA).
The company said topline data showed that ATH434 produced clinically and statistically significant improvement on the modified UMSARS Part I, a functional rating scale that assesses disability on activities of daily living affected in MSA.
ATH434 demonstrated a 48 per cent slowing of clinical progression at the 50 mg dose and 29 per cent slowing of clinical progression at the 75 mg dose at week 52 when compared with placebo.
The 75 mg dose group showed a 62 per cent slowing of progression at week 26.
Alterity said that in addition to the robust efficacy demonstrated on the UMSARS I, trends of improved motor performance were observed on the Parkinson’s Plus rating scale, and the overall benefit was shown on the Clinical Global Impression of Severity at the 50 mg dose. Biomarkers were used to evaluate potential drug effects and target engagement.
Regarding iron content by MRI, the 50 mg dose reduced iron accumulation in MSA-affected brain regions and the 75 mg dose reduced iron accumulation in the globus pallidus.
The reduced accumulation of iron was significant for the 50 mg dose group at 26 weeks and approached statistical significance at 52 weeks. Trends in preservation of brain volume were observed in the 50 mg and 75 mg groups relative to placebo at both 26 and 52 weeks of treatment.
“We are thrilled that ATH434 has demonstrated significant slowing of clinical progression and an excellent safety profile in this rare, rapidly progressive disease,” said Alterity CEO Dr David Stamler.
“Currently, there are no approved treatments that slow the progression of MSA and 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 is extremely meaningful because it assesses the functional areas affected in MSA and is the endpoint needed to support drug approval by the U.S. Food and Drug Administration (FDA).
"Based on the strength of these Phase 2 data, we look forward to engaging with the FDA as quickly as possible to discuss the path forward for accelerating the development of ATH434 given the tremendous unmet need for treating MSA. We are very grateful for the invaluable contributions of the study participants and the clinical sites who contributed to the study.”
Dr Daniel Claassen, Professor of Neurology at Vanderbilt University Medical Center and Coordinating Investigator for the ATH434-201 Phase 2 study, said, “The findings from the study are compelling because ATH434 appears to have meaningfully slowed MSA progression and stabilised motor function. To date, no treatment has altered the progression of this devastating disease. The slowing of clinical progression in this study, particularly at 50 mg, is impressive. I look forward to continue working with Alterity to bring this therapy to patients, and I know the MSA community welcomes this exciting advancement.”
Dr. Stamler added, “We now have evidence that targeting excess labile iron in neurodegenerative disease can be achieved. By redistributing this reactive form of iron that contributes to disease pathogenesis, not only can we target α-synuclein aggregation, but we can also break the vicious cycle underlying disease progression. This has implications for developing disease-modifying treatments for orphan diseases such as MSA and Friedreich’s ataxia as well as major neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease.”