Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq:
AVXL), a clinical-stage biopharmaceutical company developing
differentiated therapeutics for the treatment of neurodegenerative
and neurodevelopmental disorders including Alzheimer’s disease,
Parkinson’s disease, Rett syndrome and other central nervous system
(CNS) diseases, today announced the first entire clinical gene
pathway data from the ANAVEX®2-73-PDD-001 Parkinson’s Disease
Dementia (PDD) study at the Alzheimer’s Association International
Conference (AAIC), taking place in San Diego, CA and virtually on
July 31 – August 4, 2022.
The poster presentation titled, “Study of the
mechanism of action of Blarcamesine (ANAVEX®2-73): Whole blood
transcriptomics analysis (RNAseq) identifies treatment impact on
compensatory pathways by restoring key neurodegenerative pathways
functionality, including Alzheimer’s and Parkinson’s disease
pathways” is being presented by the principal author, Dr. Mohammad
Afshar, MD, PhD, Ariana Pharma, Paris, France and Cambridge,
US.
Randomized, placebo-controlled clinical trial in
132 patients with Parkinson’s disease dementia (PDD) included
prespecified biomarkers of response as well as Whole Exome
Sequencing DNA data and full RNA exome expression data
collection.
ANAVEX®2-73 transcriptomics analysis (RNAseq)
identified a gene network that is differentially expressed in
Parkinson’s disease dementia (PDD) patients treated with
ANAVEX®2-73 compared to placebo after 14 weeks of treatment. The
expression of 14,150 genes were analyzed from both placebo and
ANAVEX®2-73 treated patients. Biological relevance of this gene
network was assessed through pathway analysis and confirmed the
impact of ANAVEX®2-73 treatment on pathways involved in
neurodegenerative diseases, especially Alzheimer’s disease and
Parkinson’s disease.
While genes are known to be down-regulated in
Alzheimer’s disease1 and Parkinson’s disease2, representing
pathology for these diseases, ANAVEX®2-73 singularly impacted
expression levels of these genes in multiple pathways by countering
the pathological down-regulation of genes in both Alzheimer’s
(p<0.005) and Parkinson’s disease (p<0.005) and other
degenerative diseases (p<0.005).
The scope of these detected gene expressions
identified through ANAVEX®2-73 effect may represent additional
potential biomarkers of disease pathology and response.
Previously, this study demonstrated
dose-dependent, statistically significant improvement of dementia
assessment, Quality of Episodic Memory with ANAVEX®2-73 (p=0.003)
as well as significant improvement of Parkinson’s assessment,
MDS-UPDRS Total score (p=0.034), in patients treated with
ANAVEX®2-73 high oral dose once daily during the 14-week trial.
SIGMAR1 mRNA expression significantly increased in
ANAVEX®2-73-treated patients vs placebo (p=0.035) over the course
of treatment and was significantly associated with improvements of
MDS-UPDRS scores and cognitive efficacy endpoints CDR system.3
Dr. Jaime Kulisevsky, MD, PhD, Principal
Investigator of the trial, commented, "To my knowledge, this
represents the first extensive transcriptomics analysis (RNAseq) of
a therapeutic agent in patients with Parkinson’s disease dementia
(PDD). It is very intriguing to confirm this robust correlation of
the clinical improvements of motor impairment (MDS-UPDRS) and
cognition (CDR system) with compensation of expression levels of
dysregulated neurodegenerative genes, especially Alzheimer’s
disease and Parkinson’s disease, through the therapeutic effect of
ANAVEX®2-73. PDD is a debilitating disorder with significant
co-morbidities and there has not been a mechanistically novel
medication approved for PDD in over 20 years. Hence, new therapies
are urgently needed to alleviate this suffering and
disability.”
Christopher U Missling, PhD, President &
Chief Executive Officer of Anavex, stated, "It is exciting to
witness ANAVEX®2-73’s (blarcamesine) demonstration of its platform
Precision Medicine potential for both Alzheimer’s disease and
Parkinson’s disease, and likely other neurodegenerative diseases.
We believe these results will facilitate contextualization of
upcoming readout of ANAVEX®2-73 Phase 2b/3 Alzheimer’s disease
clinical trial and further supports pivotal studies in Parkinson’s
disease and Parkinson’s disease dementia. We would like to thank
all the patients and participating families as well the
investigators and clinical site coordinators for their dedication
to this study."
The presentation of the Abstract #59024 is
available on the Anavex website (www.anavex.com).
About ANAVEX®2-73-PDD-001 Clinical Study
The ANAVEX®2-73-PDD-001 study was an
international, double-blind, multicenter, placebo-controlled proof
of concept Phase 2 clinical study that randomized 132 patients with
Parkinson’s disease dementia (PDD) equally (ratio of 1:1:1) to
target doses of 30 mg, 50 mg ANAVEX®2-73 or placebo, respectively.
As previously reported, in addition to prespecified
ANAVEX®2-73-related biomarker of response, SIGMAR1, safety and
cognitive efficacy, MDS-UPDRS, actigraphy and sleep function was
assessed during the study duration of 14 weeks.
Study inclusion required diagnosis of idiopathic
Parkinson's disease (PD) consistent with the UK Parkinson's Disease
Society Brain Bank diagnostic criteria and diagnosis of probable PD
dementia (PDD) according to the Movement Disorder Society Task
Force clinical diagnostic criteria as well as Montreal Cognitive
Assessment (MoCA) score of 13 to 23. DNA and RNA from blood samples
were analyzed using NGS.
Study participants were allowed to be on stable
regimen of anti-Parkinson's disease medications (including
levodopa, dopamine agonists, MAO-B inhibitors, or entacapone).
Treatment with cholinesterase inhibitors, rivastigmine, donepezil
and galantamine (Exelon®, Aricept®, or Reminyl®) were also
permitted.
The study found that ANAVEX®2-73 was well
tolerated in oral doses up to 50 mg once daily. The results showed
clinically meaningful, dose-dependent, and statistically
significant improvements in the Cognitive Drug Research (CDR)
computerized assessment system analysis. The study validated the
precision medicine approach of targeting SIGMAR1 as a genetic
biomarker of response to ANAVEX®2-73, confirming that ANAVEX®2-73
acts through SIGMAR1 activation.
Broad and statistically significant improvements
in CDR system Cognitive Domain of Attention assessed by Choice
Reaction Time (p = 0.039) and Digital Vigilance (p = 0.008) and CDR
system Episodic Memory (p = 0.047), representing complex cognitive
tasks with impact on quality of life such as making a choice
between similar objects and remembering daily personal experiences,
which are mostly impaired in both PD and AD.4
Statistically significant dose-dependent (p =
0.003) improvement of Episodic Memory, which has been shown to be
highly correlated (70%) with the Alzheimer’s Disease Assessment
Scale–Cognitive score (ADAS-Cog; r = 0.7).5
ANAVEX®2-73 does not impair sleep and has a
positive effect on REM sleep behavior disorder.
ANAVEX®2-73 was generally safe, well tolerated,
and improved safety profile compared to dementia drugs associated
with typical adverse effects.
After completing the ANAVEX®2-73-PDD-001 trial,
participants were able to enroll in a voluntary 48-week open-label
extension study, ANAVEX®2-73-PDD-EP-001, which continued to assess
safety, long term efficacy and changes in gut microbiota.6
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a
publicly traded biopharmaceutical company dedicated to the
development of novel therapeutics for the treatment of
neurodegenerative and neurodevelopmental disorders including
Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other
central nervous system (CNS) diseases, pain, and various types of
cancer. Anavex’s lead drug candidate, ANAVEX®2-73 (blarcamesine),
has successfully completed a Phase 2a clinical trial for
Alzheimer’s disease, a Phase 2 proof-of-concept study in
Parkinson’s disease dementia and both a Phase 2 and a Phase 3 study
in adult patients with Rett syndrome. ANAVEX®2-73 is an orally
available drug candidate that restores cellular homeostasis by
targeting sigma-1 and muscarinic receptors. Preclinical studies
demonstrated its potential to halt and/or reverse the course of
Alzheimer’s disease. ANAVEX®2-73 also exhibited anticonvulsant,
anti-amnesic, neuroprotective, and anti-depressant properties in
animal models, indicating its potential to treat additional CNS
disorders, including epilepsy. The Michael J. Fox Foundation for
Parkinson’s Research previously awarded Anavex a research grant,
which fully funded a preclinical study to develop ANAVEX®2-73 for
the treatment of Parkinson’s disease. ANAVEX®3-71, which targets
sigma-1 and muscarinic M1 receptors, is a promising clinical stage
drug candidate demonstrating disease-modifying activity against the
major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD)
mice, including cognitive deficits, amyloid, and tau pathologies.
In preclinical trials, ANAVEX®3-71 has shown beneficial effects on
mitochondrial dysfunction and neuroinflammation. Further
information is available at www.anavex.com. You can also connect
with the company on Twitter, Facebook, Instagram and LinkedIn.
Forward-Looking Statements
Statements in this press release that are not
strictly historical in nature are forward-looking statements. These
statements are only predictions based on current information and
expectations and involve a number of risks and uncertainties.
Actual events or results may differ materially from those projected
in any of such statements due to various factors, including the
risks set forth in the Company’s most recent Annual Report on Form
10-K filed with the SEC. Readers are cautioned not to place undue
reliance on these forward-looking statements, which speak only as
of the date hereof. All forward-looking statements are qualified in
their entirety by this cautionary statement and Anavex Life
Sciences Corp. undertakes no obligation to revise or update this
press release to reflect events or circumstances after the date
hereof.
For Further Information:
Anavex Life Sciences Corp.Research &
Business DevelopmentToll-free: 1-844-689-3939Email:
info@anavex.com
Investors:Andrew J.
BarwickiInvestor Relations Tel: 516-662-9461 Email:
andrew@barwicki.com
____________________________________1 Liang WS,
Reiman EM, Valla J, et al. Alzheimer's disease is associated with
reduced expression of energy metabolism genes in posterior
cingulate neurons. Proc Natl Acad Sci U S A.
2008;105(11):4441-4446. doi:10.1073/pnas.0709259105; Lunnon K,
Keohane A, Pidsley R, et al. Mitochondrial genes are altered in
blood early in Alzheimer's disease. Neurobiol Aging. 2017;53:36-47.
doi:10.1016/j.neurobiolaging. 2016.12.0292 Hauser MA, Li YJ, Xu H,
et al. Expression profiling of substantia nigra in Parkinson
disease, progressive supranuclear palsy, and frontotemporal
dementia with parkinsonism. Arch Neurol. 2005;62(6):917-921.
doi:10.1001/archneur.62.6.917; Hendrickx DM, Glaab E. Comparative
transcriptome analysis of Parkinson's disease and
Hutchinson-Gilford progeria syndrome reveals shared susceptible
cellular network processes. BMC Med Genomics. 2020;13(1):114.
Published 2020 Aug 18. doi:10.1186/s12920-020-00761-63
https://www.anavex.com/post/anavex-life-sciences-announces-presentation-of-phase-2-clinical-biomarker-data-from-pdd-study4
Mahurin, R. K., & Pirozzolo, F. J. (1993). Application of
Hick’s law of response speed in Alzheimer and Parkinson diseases.
Perceptual and Motor Skills, 77(1), 107–1135 Wesnes K, Edgar C,
Andreasen N, Annas P, Basun H, Lannfelt L, et al. Computerized
cognition assessment during acetylcholinesterase inhibitor
treatment in Alzheimer’s disease. Acta Neurol Scand 2010;
122:270–76 ClinicalTrials.gov Identifier: NCT04575259
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