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 interim data from the ATH434-202 open-label
Phase 2 clinical trial in patients with multiple system atrophy
(MSA). ATH434 has been shown preclinically to reduce α-synuclein
pathology and preserve neuronal function by restoring normal iron
balance in the brain.
The interim analysis included clinical and
biomarker data on 7 participants treated with ATH434 for 6 months
and neuroimaging data on 3 participants who were treated for 12
months. After 6 months of treatment, 43% of participants showed
improvement on the UMSARS1, indicating reduced disability on
activities of daily living. Over the same period, 29% of
participants had stable or improved neurological symptoms (clinical
responders) as assessed by both the treating physician and the
patient. Importantly, the clinical responders on average had
reduced accumulation of iron on MRI in the substantia nigra,
putamen and globus pallidus and stable levels of NFL, a marker of
axonal injury, when compared to participants who declined.
“I am very encouraged by these positive interim
data in advanced MSA patients,” said David Stamler, M.D., Chief
Executive Officer of Alterity. “As MSA is a rapidly progressive and
unremitting disease, we expected to see decline in all
participants. Instead, we saw favorable clinical and biomarker
outcomes in some patients suggesting that ATH434 has the potential
to modify the course of this devastating condition. We were also
very pleased to see that the clinical responders had biomarker
evidence of stable disease as this provides an objective indication
of potential efficacy.”
Dr. Stamler, continued, “In the ATH434-202
trial, the participants who stabilized or improved with ATH434
treatment had less advanced disease than those who progressed. This
is noteworthy as we have enrolled earlier stage MSA patients in our
randomized, double-blind clinical trial ATH434-201. Although the
number of patients studied thus far is small, the new data
reinforces that we have taken the right approach in our randomized
trial and increases my overall confidence in the ATH434 development
program.”
Daniel Classen, M.D., M.S., Professor of
Neurology at Vanderbilt University Medical Center and principal
investigator for the ATH434-202 Phase 2 study, commented “I am
gratified to see that the work we have done over the last several
years is bearing fruit as we enhance our understanding of MSA. This
has led to improved patient selection and optimized biomarker
endpoints in the Alterity Phase 2 trials. The clinical observations
in the ATH434-202 study are supported by the objective biomarkers
of brain volume, brain iron, and NfL. These early data increase our
confidence that we have chosen the right biomarker and clinical
endpoints to evaluate the potential effect of ATH434 in individuals
with MSA. I am grateful to the study participants and their family
members for their contributions to the study.”
ATH434-202 Interim Results
A total of 10 participants have been enrolled in
the trial. The interim data reported today is from the 7 patients
who have completed six months of treatment with ATH434, 3 of whom
have also completed 12 months of treatment. Only neuroimaging data
are available from month 12. The participants in the trial were
diagnosed with MSA using a multimodal approach (clinical,
neuroimaging, fluid biomarkers) and treated with oral ATH434 75 mg
twice daily.
Clinical, biomarker and safety assessments were
conducted during the study. While the data are preliminary, the
Company sees a positive trend with the current participant patient
outcomes.
Clinical Assessments at Month 6
Unified MSA Rating Scale Part I, historical
review (UMSARS)
- 43% (3/7) of
participants had lower scores (improvement) on the UMSARS that
assesses activities of daily living affected in MSA, such as
speech, swallowing, walking and urinary/bowel function.
- In the trial,
mean (SD) UMSARS scores (N=7) increased from baseline to 6 months
by 1.7 (5.1) points. These study data compare favorably to
historical data in a similar MSA population that demonstrated an
increase of 3.9 (4.6) points over 6 months.2
Global Impression of Change
- 29% (2/7) of
participants stabilized or improved on the Clinical Global
Impression of Change (CGIC) scale, which asks the investigator to
evaluate overall neurological symptoms as compared to immediately
before starting therapy.
- 29%
(2/7) of participants also stabilized or improved on the Patient
Global Impression of Change (PGIC) scale which asks the patient to
evaluate their overall neurological symptoms as compared to
immediately before starting therapy.
Safety
- In general,
ATH434 was well tolerated by study participants and most adverse
events were mild to moderate in severity.
- No serious
adverse events related to study drug were reported.
Biomarker Assessments at Month 6 and Month
12
MRI Biomarkers (n=7):
- Brain Volume:
- At Month 6, there were similar
declines in brain volume, as assessed by the MSA-atrophy index
(MSA-AI)3 in all participants consistent with the nature of
MSA.
- However, in the clinical
responders, brain volume assessed by the MSA-AI was stable between
Month 6 and Month 12.
- Iron content in the substantia
nigra was stable over 12 months in the clinical responders.
- Myoinositol is an exploratory
biomarker of glial cell pathology in MSA. Treatment with ATH434 led
to smaller increases in myoinositol in clinical responders compared
to participants who worsened.
Fluid Biomarkers (n=5):
- Neurofilament
Light Chain (NfL) is a marker of axonal injury in neurons and has
been shown to correlate with disease severity in many neurological
diseases. In the trial, clinical responders had stable spinal fluid
NfL levels on average whereas those who declined clinically had
increased spinal fluid NfL levels.
Definitions and References
1 Unified MSA Rating Scale, Part I (historical review). Areas
assessed include: Speech, swallowing, handwriting, cutting
food/handling utensils, dressing, hygiene, walking, falling,
orthostatic symptoms, urinary function, sexual function and bowel
function.
2 Wenning et al. The natural history of multiple system atrophy:
a prospective European cohort study. Lancet Neurol 2013; 12:
264–74.
3 MSA Atrophy Index: This index measures the degree of atrophy
relative to a normal population, with more negative values
indicating greater atrophy
About ATH434-202 Phase 2 Clinical
Trial
The ATH434-202 Phase 2 clinical trial is an open
label study, entitled “A Biomarker Study of ATH434 in
Participants with MSA.” The Biomarker trial enrolled 10 individuals
with advanced MSA. ATH434-202 study participants will receive
treatment with ATH434 for 12-months. The study will assess the
effect of ATH434 treatment on neuroimaging and protein biomarkers
to evaluate target engagement, in addition to clinical measures,
safety, and pharmacokinetics. The selected biomarkers, including
brain volume, iron and aggregating α-synuclein, are important
contributors to MSA pathology and are appropriate targets to
demonstrate drug activity. The primary objective of this study is
to evaluate the impact of 12 months treatment with ATH434 on brain
volume in a more advanced patient population than is being studied
in Alterity’s randomized Phase 2 trial. Final, 12-month data from
the ATH434-202 trial are expected in the first half of 2025.
Additional information on the open label Phase 2 trial can be found
at clinicaltrials.gov NCT05864365.
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 is
currently being studied in two clinical trials: Study ATH434-201 is
a randomized, double-blind, placebo-controlled Phase 2 clinical
trial in patients with early-stage MSA and Study ATH434-202 is an
open-label Phase 2 Biomarker trial in patients with more advanced
MSA. 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 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.1
1Multiple System Atrophy | National Institute of Neurological
Disorders and Stroke (nih.gov)
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’s
lead asset, ATH434, has the potential to treat various Parkinsonian
disorders and is currently being evaluated in two Phase 2 clinical
trials in Multiple System Atrophy. Alterity also 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
web site at www.alteritytherapeutics.com.
Authorisation & Additional informationThis
announcement was authorized by David Stamler, CEO of Alterity
Therapeutics Limited.
Investor and Media Contacts:
AustraliaHannah
Howlettwe-aualteritytherapeutics@we-worldwide.com+61 450 648
064
U.S.Remy Bernardaremy.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,"
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Important factors that could cause actual
results to differ materially from those indicated by such
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most recent Annual Report on Form 20-F as well as reports on Form
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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
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whether written or oral, that may be made from time to time,
whether as a result of new information, future developments or
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