Alterity Therapeutics Limited【ATHE】株式ニュース

Alterity Therapeutics Announces Positive ATH434 Phase 2 Trial Results in Multiple System Atrophy Led By Robust Clinical Efficacy
– Clinically Meaningful Benefit Observed at Both ATH434 Doses Studied –

– Achieved Statistical Significance with Up to 48% Slowing of Clinical Progression on UMSARS Rating Scale –

– Key MRI Biomarker Shows Iron Stabilization in MSA Affected Brain Regions –

– ATH434 Demonstrated a Favorable Safety Profile –

– Webcast Held Yesterday with Access to the Recording Below –

MELBOURNE, Australia and SAN FRANCISCO, Jan. 30, 2025 (GLOBE NEWSWIRE) -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, today announced positive topline results from the ATH434-201 randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage multiple system atrophy (MSA).

The 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 MSA1. On this important clinical measure, ATH434 demonstrated 48% slowing of clinical progression at the 50 mg dose (p=0.03)^ and 29% slowing of clinical progression at the 75 mg dose (p=0.2) at Week 52 when compared with placebo. The 75 mg dose group showed a 62% slowing of progression (p=0.05) at Week 26. In addition to the robust efficacy demonstrated on the UMSARS I, trends of improved motor performance were observed on the Parkinson’s Plus rating scale2 and overall benefit was shown on the Clinical Global Impression of Severity at the 50 mg dose (p=0.009).

Biomarkers were used to evaluate potential drug effect and target engagement. Regarding iron content by MRI, the 50 mg dose reduced iron accumulation in MSA affected brain regions (substantia nigra, putamen, and globus pallidus) 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 (putamen, P=0.025) and approached statistical significance at 52 weeks (globus pallidus, P=0.08). 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 David Stamler, M.D., Chief Executive Officer of Alterity. “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.”

Daniel Claassen, M.D., M.S., Professor of Neurology at Vanderbilt University Medical Center and Coordinating Investigator for the ATH434-201 Phase 2 study, commented “The findings from the study are compelling because ATH434 appears to have meaningfully slowed MSA progression and stabilized 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 concluded, “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 a-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.”

Webcast details

The webcast recording can be accessed on the Events and Presentation page of the Company’s website here.

ATH434-201 Topline Data Summary

The ATH434-201 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled investigation of 12 months treatment with ATH434 in participants with early-stage MSA. The trial enrolled globally with 23 sites in six countries. The study evaluated the efficacy, safety and pharmacokinetics of ATH434 as well as the effect of ATH434 on neuroimaging and protein biomarkers. Wearable movement sensors were employed to evaluate motor activities in an outpatient setting. The study enrolled 77 adults who were randomly assigned to receive one of two dose levels of ATH434 (50mg or 75mg) or placebo. Treatment was administered orally twice-a-day (BID).

ATH434 Efficacy Results (n=61)
The principal efficacy analyses were performed on the modified Intent-to-Treat (mITT) population, which includes enrolled participants who received study drug and had at least one MRI evaluation for brain iron at six months. There were approximately 20 patients per arm in the mITT. Both clinical doses demonstrated improvement relative to placebo over 52 weeks, with the 50 mg dose showing a greater treatment effect. Additional analyses are ongoing to understand the differences between the two groups.

Key Biomarker Endpoint:
On the primary endpoint of iron content by MRI, ATH434 demonstrated reduced or stabilized iron content in key brain regions affected by MSA.

Demonstrated target engagement of ATH434
The 50 mg dose reduced iron accumulation in the substantia nigra, putamen, and globus pallidus The reduced accumulation of iron was significant at 26 weeks (putamen, P=0.025) and approached statistical significance at 52 weeks (globus pallidus, P=0.08)
The 75 mg dose reduced iron accumulation in the globus pallidus
Other biomarkers were used to evaluate potential drug effect and target engagement.

Brain Volume: ATH434 demonstrated a trend in preserving brain volume as compared to placebo at both 50 mg and 75 mg dose levels, as assessed by the MSA atrophy index (MSA-AI)3
NfL: The analysis of neurofilament light chain (NfL) levels in spinal fluid is ongoing
Key Clinical Endpoint: UMSARS Part I
The key secondary endpoint was defined as the change in the Unified MSA Rating Scale Part I (UMSARS I). UMSARS I is a functional rating scale that assesses disability and disease severity in MSA. It is the most meaningful endpoint in the trial, as it is the clinical endpoint of interest to support approval by regulatory authorities such as the FDA.

Placebo treated patients declined by a mean of 4.5 points over 26 weeks and 8.2 points over 52 weeks
The 50 mg dose declined by a mean of 4.3 points over 52 weeks, equivalent to a 48% slowing of clinical progression (p=0.03)
The 75 mg dose declined by a mean of 5.8 points over 52 weeks, equivalent to a 29% slowing of clinical progression (p=0.2)
The 75 mg dose declined by a mean of 1.8 points over 26 weeks equivalent to a 62% slowing of clinical progression (p=0.05)
Both dose groups clearly separated from placebo.
Additional Secondary Endpoints:
Observed trends of improved motor performance support the efficacy of ATH434 in the clinical setting:

Clinical Global Impression of Severity4 (7-point scale, higher score worse) Mean change at 50 mg: -0.81 (p=0.009)Mean change at 75 mg: -0.18 (p=NS)
Parkinson Plus total motor scale: Trends in both dose groups at 26 and 52 weeks with a clinical benefit apparent in multiple domains
Increased activity on wearable sensors in both groups with increases in step count, bouts of walking, total walking time, and standing time
Orthostatic Hypotension Symptom Assessment (patient rated) showed trends favoring benefit in both groups (p=0.13 at 50 mg)
ATH434 Safety Results (n=77)
The safety population includes all enrolled participants who received at least one dose of study drug. Overall, 26 participants received the 50 mg dose, 25 participants received the 75 mg dose, and 26 participants received placebo.

ATH434 was well-tolerated with similar adverse event (AE) rates in ATH434 treatment groups and placebo
Most AEs were mild to moderate in severity
No serious adverse events (SAEs) related to ATH434 were reported
Discontinuations for AEs were similar in the placebo (n=3) and 75 mg dose (n=5) groups and lowest at 50 mg (n=0). None of the AEs leading to discontinuation were related to treatment.
About ATH434

Alterity’s lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown preclinically to reduce a-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain. As an iron chaperone, it has excellent potential to treat Parkinson’s disease as well as various Parkinsonian disorders such as Multiple System Atrophy (MSA). ATH434 successfully completed Phase 1 studies demonstrating the agent is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA. ATH434 recently announced positive results from the randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA. A second Phase 2 open-label 2 Biomarker trial in patients with more advanced MSA is ongoing. ATH434 has been granted Orphan Drug Designation for the treatment of MSA by the U.S. FDA and the European Commission.

About Multiple System Atrophy

Multiple System Atrophy (MSA) is a rare, neurodegenerative disease characterized by failure of the autonomic nervous system and impaired movement. The symptoms reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord. It is a rapidly progressive disease and causes profound disability. MSA is a Parkinsonian disorder characterized by a variable combination of slowed movement and/or rigidity, autonomic instability that affects involuntary functions such as blood pressure maintenance and bladder control, and impaired balance and/or coordination that predisposes to falls. A pathological