Alterity Therapeutics Presents Encouraging New Data from its ATH434 Phase 2 Trial in Multiple System Atrophy at the American Academy of Neurology Annual Meeting
Alterity Therapeutics (NASDAQ: ATHE) has presented new data from its ATH434 Phase 2 trial for Multiple System Atrophy (MSA) at the American Academy of Neurology 2025 Annual Meeting. The double-blind study showed promising results with clinically meaningful efficacy across multiple measures.
Key findings include:
- 48% decrease in clinical progression at 50mg dose (p=0.02) and 30% decrease at 75mg dose using modified UMSARS I rating scale
- Improvement in Clinical Global Impression of Severity Scale at 50mg dose (p=0.0088)
- Positive trends in Orthostatic Hypotension Symptom Assessment
- Increased activity levels measured by wearable sensors, including improved step count, walking time, and standing time
The imaging outcomes in 61 participants demonstrated that ATH434 reduces iron signal in MSA-affected brain regions. Additionally, results from the bioMUSE natural history study supported the utility of wearable sensors in MSA trials, showing correlations between sensor-derived metrics and clinical evaluations.
Alterity Therapeutics (NASDAQ: ATHE) ha presentato nuovi dati dal suo studio di Fase 2 ATH434 per l'Atrofia Muscolare Multipla (MSA) durante il Congresso Annuale dell'Accademia Americana di Neurologia 2025. Lo studio in doppio cieco ha mostrato risultati promettenti con un'efficacia clinicamente significativa su molteplici parametri.
I risultati chiave includono:
- Riduzione del 48% nella progressione clinica con la dose di 50mg (p=0.02) e del 30% con la dose di 75mg utilizzando la scala di valutazione UMSARS I modificata
- Miglioramento nella Scala di Impressione Clinica della Gravità con la dose di 50mg (p=0.0088)
- Tendenze positive nella Valutazione dei Sintomi dell'Ipotensione Ortostatica
- Aumento dei livelli di attività misurati tramite sensori indossabili, inclusi miglioramenti nel conteggio dei passi, nel tempo di camminata e nel tempo in piedi
I risultati di imaging su 61 partecipanti hanno dimostrato che ATH434 riduce il segnale di ferro nelle aree cerebrali colpite dalla MSA. Inoltre, i risultati dello studio di storia naturale bioMUSE hanno sostenuto l'utilità dei sensori indossabili negli studi sulla MSA, mostrando correlazioni tra le metriche derivate dai sensori e le valutazioni cliniche.
Alterity Therapeutics (NASDAQ: ATHE) ha presentado nuevos datos de su ensayo de Fase 2 ATH434 para la Atrofia Muscular Múltiple (MSA) en la Reunión Anual de la Academia Americana de Neurología 2025. El estudio doble ciego mostró resultados prometedores con una eficacia clínicamente significativa en múltiples medidas.
Los hallazgos clave incluyen:
- Reducción del 48% en la progresión clínica con la dosis de 50mg (p=0.02) y del 30% con la dosis de 75mg utilizando la escala de calificación UMSARS I modificada
- Mejora en la Escala de Impresión Global Clínica de Severidad con la dosis de 50mg (p=0.0088)
- Tendencias positivas en la Evaluación de Síntomas de Hipotensión Ortostática
- Aumento de los niveles de actividad medidos por sensores portátiles, incluyendo mejoras en el conteo de pasos, el tiempo de caminata y el tiempo de pie
Los resultados de imagen en 61 participantes demostraron que ATH434 reduce la señal de hierro en las regiones cerebrales afectadas por la MSA. Además, los resultados del estudio de historia natural bioMUSE apoyaron la utilidad de los sensores portátiles en los ensayos de MSA, mostrando correlaciones entre las métricas derivadas de los sensores y las evaluaciones clínicas.
Alterity Therapeutics (NASDAQ: ATHE)는 2025년 미국 신경학회 연례 회의에서 다계통 위축증(MSA)을 위한 ATH434 2상 시험의 새로운 데이터를 발표했습니다. 이 이중 맹검 연구는 임상적으로 의미 있는 효능을 여러 측정에서 보여주는 유망한 결과를 나타냈습니다.
주요 발견 사항은 다음과 같습니다:
- 50mg 용량에서 임상 진행이 48% 감소(p=0.02), 75mg 용량에서 30% 감소(수정된 UMSARS I 평가 척도 사용)
- 50mg 용량에서 중증도에 대한 임상 전반적 인상 개선(p=0.0088)
- 기립성 저혈압 증상 평가에서 긍정적인 경향
- 웨어러블 센서를 통해 측정된 활동 수준 증가, 개선된 걸음 수, 걷는 시간 및 서 있는 시간 포함
61명의 참가자에서의 영상 결과는 ATH434가 MSA에 영향을 받은 뇌 영역에서 철 신호를 줄인다는 것을 보여주었습니다. 또한, bioMUSE 자연사 연구의 결과는 MSA 시험에서 웨어러블 센서의 유용성을 뒷받침하며, 센서에서 유도된 지표와 임상 평가 간의 상관관계를 보여주었습니다.
Alterity Therapeutics (NASDAQ: ATHE) a présenté de nouvelles données de son essai de Phase 2 ATH434 pour l'Atrophie Systémique Multiple (MSA) lors de la Réunion Annuelle de l'Académie Américaine de Neurologie 2025. L'étude en double aveugle a montré des résultats prometteurs avec une efficacité cliniquement significative sur plusieurs mesures.
Les résultats clés comprennent:
- Une diminution de 48% de la progression clinique à la dose de 50mg (p=0.02) et une diminution de 30% à la dose de 75mg utilisant l'échelle de notation UMSARS I modifiée
- Amélioration de l'Échelle d'Impression Globale Clinique de Sévérité à la dose de 50mg (p=0.0088)
- Tendances positives dans l'Évaluation des Symptômes d'Hypotension Orthostatique
- Niveaux d'activité accrus mesurés par des capteurs portables, y compris une amélioration du nombre de pas, du temps de marche et du temps debout
Les résultats d'imagerie chez 61 participants ont démontré qu'ATH434 réduit le signal de fer dans les régions cérébrales affectées par la MSA. De plus, les résultats de l'étude bioMUSE sur l'histoire naturelle ont soutenu l'utilité des capteurs portables dans les essais sur la MSA, montrant des corrélations entre les métriques dérivées des capteurs et les évaluations cliniques.
Alterity Therapeutics (NASDAQ: ATHE) hat auf dem Jahrestreffen der American Academy of Neurology 2025 neue Daten aus seiner ATH434 Phase 2-Studie zur Multiplen Systematrophie (MSA) vorgestellt. Die doppelblinde Studie zeigte vielversprechende Ergebnisse mit klinisch bedeutsamer Wirksamkeit in mehreren Maßstäben.
Wichtige Ergebnisse umfassen:
- 48% Rückgang der klinischen Progression bei 50mg Dosis (p=0.02) und 30% Rückgang bei 75mg Dosis unter Verwendung der modifizierten UMSARS I Bewertungsskala
- Verbesserung der Clinical Global Impression of Severity Scale bei 50mg Dosis (p=0.0088)
- Positive Trends in der Bewertung der Symptome der orthostatischen Hypotonie
- Erhöhte Aktivitätsniveaus, gemessen mit tragbaren Sensoren, einschließlich verbesserter Schrittzahl, Gehzeit und Stehzeit
Die Bildgebungsresultate bei 61 Teilnehmern zeigten, dass ATH434 das Eisen-Signal in von MSA betroffenen Gehirnregionen reduziert. Darüber hinaus unterstützten die Ergebnisse der bioMUSE-Studie zur natürlichen Geschichte die Nützlichkeit tragbarer Sensoren in MSA-Studien und zeigten Korrelationen zwischen sensorbasierten Metriken und klinischen Bewertungen.
- 48% reduction in disease progression at 50mg dose (p=0.02)
- Statistically significant improvement in severity scale at 50mg dose (p=0.0088)
- Demonstrated target engagement through reduced iron signals in brain
- Increased patient mobility confirmed by wearable sensor data
- 75mg dose showed lower efficacy (30%) compared to 50mg dose (48%)
- Some measures only showed trends rather than statistical significance
Insights
Alterity's ATH434 Phase 2 results represent a significant advancement in MSA treatment development. The 48% reduction in clinical progression at the 50mg dose (p=0.02) on the modified UMSARS I scale is particularly impressive for a neurodegenerative condition with no approved disease-modifying therapies.
What makes these results compelling is the consistency across multiple endpoints. Beyond the primary functional measure, improvements were observed in clinical global impression severity (p=0.0088 at 50mg), orthostatic hypotension symptoms, and objectively measured physical activity via wearable sensors. Most critically, the neuroimaging data confirmed target engagement by demonstrating reduced iron signal in MSA-affected brain regions, validating the drug's proposed mechanism of action.
The dose response pattern is intriguing, with the 50mg dose outperforming the 75mg dose (48% vs 30% reduction in progression). This inverted dose-response suggests optimal efficacy might occur at lower concentrations, which could have favorable implications for the safety profile, though safety data wasn't explicitly detailed in this presentation.
The bioMUSE natural history study results provide additional validation for using digital biomarkers in MSA clinical assessment, strengthening the relevance of the wearable sensor findings in the interventional trial.
These findings position ATH434 as a promising candidate for further development in MSA, a rare and devastating neurodegenerative disorder with substantial unmet medical need.
Alterity's Phase 2 ATH434 data represents a meaningful clinical milestone that significantly enhances the company's development pipeline. The statistically significant 48% reduction in disease progression at the 50mg dose addresses a critical unmet need in MSA, a rare neurodegenerative disorder with no approved disease-modifying treatments.
Several aspects of these results particularly stand out from an investment perspective. First, the multi-modal evidence of efficacy across different assessment types (clinician-rated scales, patient-reported outcomes, and objective digital measures) creates a robust dataset that reduces the risk profile for future development stages. Second, the confirmation of target engagement through neuroimaging provides mechanistic validation that strengthens the scientific case.
For a small-cap biotech like Alterity (market cap: $28.5M), these positive Phase 2 results could serve as a significant value inflection point. The company's planned regulatory engagement suggests confidence in the data package and could potentially lead to discussions about expedited development pathways given the serious unmet need in MSA.
While Phase 3 studies will still be required, these results substantially de-risk the program and strengthen Alterity's position for potential partnering discussions or additional financing to support late-stage development. The wearable sensor data also offers a potential competitive advantage in assessment methodology for future trials.
– Clinically Meaningful Efficacy Observed on Multiple Assessments –
– Confirmed Target Engagement with Reduced Iron Signal in MSA Affected Brain Regions –
MELBOURNE, Australia and SAN FRANCISCO, April 10, 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 that new presentations related to its Multiple System Atrophy (MSA) program were delivered at the American Academy of Neurology (AAN) 2025 Annual Meeting, one of the premier global neurology meetings. Notably, new data from the ATH434-201 trial was prominently featured via an oral presentation during a Scientific Platform Session on Movement Disorders.
“We are excited to present these new data from our double-blind Phase 2 trial, reinforcing the potential of ATH434 to significantly modify disease progression in MSA. The clinical results from this study are important given the lack of available treatments to address the underlying pathology in MSA,” said, David Stamler, M.D., Chief Executive Officer of Alterity. “Importantly, we saw clinically meaningful efficacy on multiple measures including the UMSARS1 I activities of daily living scale, the clinical global impression of severity, the orthostatic hypotension symptom assessment, and activity levels from wearable sensors. In addition, new analyses of neuroimaging data show target engagement of ATH434 on iron levels in MSA affected regions of the brain. We look forward to engaging with the U.S. Food and Drug Administration and other regulatory authorities as we seek to advance the development of this potentially disease modifying therapy for individuals living with MSA.”
“In addition, results from the bioMUSE natural history study were presented by our collaborators at Vanderbilt University Medical Center on the use of wearable sensors to assess outpatient activity. These data support the utility of digital outcomes in MSA trials and reinforce the relevance of the findings in our double-blind trial,” concluded Dr. Stamler.
Type: Oral Presentation
Title: Topline Data from a Randomized, Double Blind, Placebo Controlled Phase 2 Study of ATH434 in Multiple System Atrophy
Presenter: Daniel Claassen, M.D., M.S., Professor of Neurology at Vanderbilt University Medical Center
Summary: The oral presentation produced additional data on Alterity’s ATH434-201 Phase 2 clinical trial. Overall, the study results support continued advancement of ATH434 for the treatment of MSA. The imaging outcomes in n=61 participants indicate a heterogeneous localization of pathology and evidence that ATH434 reduces the iron signal in MSA affected brain regions. The clinical analysis included 71 patients who had at least one-post baseline UMSARS I assessment. The data showed that on the modified UMSARS I rating scale, ATH434 demonstrated a clinically significant treatment effect versus placebo with a
Type: Poster Presentation
Title: Association Between Wearable Sensor Data and Clinical Scores in Individuals with Early-stage Multiple System Atrophy
Presenter: Ashkan Vaziri, PhD, BioSensics LLC
Summary: The poster described the n=18 patients with clinically probable MSA who wore sensors for continuous monitoring of physical activity during our bioMUSE natural history study. The study determined the association between gold-standard clinical measures and sensor-derived parameters of locomotion, posture, and postural transitions at baseline. From this, machine learning models were developed to investigate whether sensor-derived measures could predict scores and performance on clinical evaluations. The study found that sensor-derived metrics, specifically those measuring walking and postural transitions, may increase the understanding of impairments associated with MSA. Across several tests, the participants who had increased walking time, walking episodes, and higher step counts had better scores on the tandem walk and Timed Up and Go (TUG). Additionally, positive relationships were identified between the average sit-to-stand and stand-to-sit durations with motor rating scales such as the MSA Rating Scale (UMSARS-II), the motor section of the Parkinson’s Plus Rating Scale (NNIPPS-PPS3), and the TUG. Importantly, regression models established successful prediction of clinical scores, with TUG demonstrating the highest explained variance.
The poster presentations will be available on the Alterity website here.
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 α-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 ATH434-201 Phase 2 Clinical Trial
The ATH434-201 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled investigation of 12 months treatment with ATH434 in patients with MSA. The study evaluated the efficacy, safety and pharmacokinetics of ATH434 as well as the effect of ATH434 on neuroimaging and protein biomarkers. Wearable sensors were employed to evaluate motor activities outside of the clinic. The study enrolled 77 adults who were randomly assigned to receive ATH434 50 mg or 75 mg twice daily or matching placebo. 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 MSA. In addition to the robust efficacy demonstrated on the UMSARS Part I, trends in improved motor performance were observed on the Parkinson’s Plus rating scale and overall benefit was shown on the Clinical Global Impression of Severity at the 50 mg dose. Wearable sensor data indicated that both dose levels of ATH434 led to increased activity in an outpatient setting as compared to placebo. Biomarkers were used to evaluate potential drug effect and target engagement. Both dose levels reduced iron accumulation in MSA affected brain regions and trends in preservation of brain volume were observed relative to placebo. Additional information on the Phase 2 trial can be found by ClinicalTrials.gov Identifier: NCT05109091.
About bioMUSE
Biomarkers of progression in Multiple System Atrophy (bioMUSE) is a natural history study that aims to track the progression of individuals with MSA, a parkinsonian disorder without approved therapy. The study is being conducted in collaboration with Vanderbilt University Medical Center in the U.S. under the direction of Daniel Claassen, M.D., M.S., Professor of Neurology and Principal Investigator. Natural history studies are important for characterizing disease progression in selected patient populations. The study has provided rich data for optimizing the design of Alterity’s randomized ATH434-201 Phase 2 clinical trial and enrolled approximately 20 individuals with clinically probable or clinically established MSA. BioMUSE continues to provide vital information on early stage MSA patients, informs the selection of biomarkers suitable to evaluate target engagement and preliminary efficacy, and delivers clinical data to characterize disease progression in a patient population that mirrors those currently enrolling in the Phase 2 clinical trial.
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 hallmark of MSA is the accumulation of the protein α-synuclein within glia, the support cells of the central nervous system, and neuron loss in multiple brain regions. MSA affects at least 15,000 individuals in the U.S., and while some of the symptoms of MSA can be treated with medications, currently there are no drugs that are able to slow disease progression and there is no cure.4
About Alterity Therapeutics Limited
Alterity Therapeutics is a clinical stage biotechnology company dedicated to creating an alternate future for people living with neurodegenerative diseases. The Company is initially focused on developing disease modifying therapies in Parkinson’s disease and related disorders. Alterity recently reported positive data for its lead asset, ATH434, in a Phase 2 clinical trial in participants with Multiple System Atrophy (MSA), a rare and rapidly progressive Parkinsonian disorder. ATH434 is also being evaluated in a Phase 2 clinical trial in advanced MSA. In addition, Alterity has a broad drug discovery platform generating patentable chemical compounds to treat the underlying pathology of neurological diseases. The Company is based in Melbourne, Australia, and San Francisco, California, USA. For further information please visit the Company’s website at www.alteritytherapeutics.com.
References:
1 UMSARS: Unified Multiple System Atrophy Rating Scale
^ All p-values are uncorrected
2 Clinical Global Impression of Severity: a clinician assessment of the total picture of the subject including the impact of the illness on function and level of distress
3 NNIPPS-PPS: Natural History and Neuroprotection in Parkinson Plus Syndromes - Parkinson Plus Scale
4 Multiple System Atrophy | National Institute of Neurological Disorders and Stroke (nih.gov)
Authorisation & Additional information
This announcement was authorized by David Stamler, CEO of Alterity Therapeutics Limited.
Investor and Media Contacts:
Australia
Ana Luiza Harrop
we-aualteritytherapeutics@we-worldwide.com
+61 452 510 255
U.S.
Remy Bernarda
remy.bernarda@iradvisory.com
+1 (415) 203-6386
Forward Looking Statements
This press release contains "forward-looking statements" within the meaning of section 27A of the Securities Act of 1933 and section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use of such words as "expects," "intends," "hopes," "anticipates," "believes," "could," "may," "evidences" and "estimates," and other similar expressions, but these words are not the exclusive means of identifying such statements.
Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described in the sections titled “Risk Factors” in the Company’s filings with the SEC, including its most recent Annual Report on Form 20-F as well as reports on Form 6-K, including, but not limited to the following: statements relating to the Company's drug development program, including, but not limited to the initiation, progress and outcomes of clinical trials of the Company's drug development program, including, but not limited to, ATH434, and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to the difficulties or delays in financing, development, testing, regulatory approval, production and marketing of the Company’s drug components, including, but not limited to, ATH434, the ability of the Company to procure additional future sources of financing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug compounds, including, but not limited to, ATH434, that could slow or prevent products coming to market, the uncertainty of obtaining patent protection for the Company's intellectual property or trade secrets, the uncertainty of successfully enforcing the Company’s patent rights and the uncertainty of the Company freedom to operate.
Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
FAQ
What were the main efficacy results of ATHE's ATH434 Phase 2 trial in MSA?
How did ATH434 affect patient mobility in the ATHE Phase 2 trial?
What evidence of target engagement was shown in ATHE's ATH434 trial?
What were the findings from ATHE's bioMUSE study using wearable sensors?
