Alterity Therapeutics Announces Positive ATH434 Phase 2 Trial Results in Multiple System Atrophy Led By Robust Clinical Efficacy

Clinical Trial Results - ATH434 demonstrated a 48% slowing of clinical progression at the 50 mg dose and 29% at the 75 mg dose on the UMSARS Part I scale at Week 52 compared to placebo [2] - The 75 mg dose showed a 62% slowing of progression at Week 26 [2] - ATH434 reduced iron accumulation in key brain regions affected by MSA, with significant results at 26 weeks for the 50 mg dose (putamen, P=0.025) and approaching significance at 52 weeks (globus pallidus, P=0.08) [3][11] - Trends in preservation of brain volume were observed in both dose groups relative to placebo at 26 and 52 weeks [3] Biomarker and Clinical Endpoints - ATH434 demonstrated reduced or stabilized iron content in key brain regions affected by MSA, as measured by MRI [8] - The 50 mg dose reduced iron accumulation in the substantia nigra, putamen, and globus pallidus, while the 75 mg dose reduced accumulation in the globus pallidus [11] - Trends of improved motor performance were observed on the Parkinson's Plus rating scale and Clinical Global Impression of Severity at the 50 mg dose (p=0.009) [2][11] - Wearable sensors showed increased activity in both dose groups, including step count, walking bouts, total walking time, and standing time [11] Safety and Tolerability - ATH434 demonstrated a favorable safety profile with no serious adverse events (SAEs) related to the treatment reported [17] - Adverse events (AEs) were mostly mild to moderate, and discontinuation rates due to AEs were similar across placebo and treatment groups [17] - The 50 mg dose group had no discontinuations due to AEs, while the 75 mg dose group had 5 discontinuations, none of which were related to treatment [17] Study Design and Population - The ATH434-201 Phase 2 trial was a randomized, double-blind, placebo-controlled study involving 77 adults with early-stage MSA across 23 sites in six countries [6] - Participants were randomized to receive either 50 mg, 75 mg of ATH434, or placebo, administered orally twice daily [6] - The modified Intent-to-Treat (mITT) population included 61 participants who received the study drug and had at least one MRI evaluation for brain iron at six months [7] Company and Drug Overview - ATH434 is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration, with potential to treat Parkinson's disease and Parkinsonian disorders like MSA [13] - ATH434 has been granted Orphan Drug Designation for MSA by the U.S. FDA and the European Commission [13] - Alterity Therapeutics is a clinical-stage biotechnology company focused on developing disease-modifying treatments for neurodegenerative diseases, with ATH434 as its lead candidate [15] Disease Background - Multiple System Atrophy (MSA) is a rare, rapidly progressive neurodegenerative disease with no approved treatments to slow its progression [14] - MSA affects at least 15,000 individuals in the U.S. and is characterized by autonomic nervous system failure, impaired movement, and accumulation of α-synuclein protein in the brain [14]