Anavex’s Phase 2b/3 Trial of Blarcamesine (ANAVEX®2-73) in Patients with Alzheimer’s Disease Shows Robust Clinical Efficacy and Slows Neurodegeneration
September 14 2023 - 6:30AM
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 announced today that a follow-on
analysis of the landmark Phase 2b/3 study to treat early
Alzheimer’s disease with the investigational drug blarcamesine
(ANAVEX®2-73) did demonstrate a statistically significant slowing
in cognitive decline associated with Alzheimer’s disease.
The clinical effect was complemented by two
independent biomarkers: A significant reduction in pathological
amyloid beta levels in plasma1, as well as a significant slowing in
the rate of pathological brain atrophy2 on MRI (Magnetic Resonance
Imaging)3 scans.
The trial was a Multicenter (52 medical research
centers/hospitals in 5 countries), randomized, double-blind,
placebo-controlled, 48-week phase 2b/3 trial that enrolled 508
participants with early symptomatic Alzheimer disease (mild
cognitive impairment/mild dementia). Participants were randomized
to receive blarcamesine (n = 338) or placebo (n = 170) oral
capsules once daily for 48 weeks.
All prespecified clinical endpoints were
analyzed using a mixed model for repeated measures (MMRM). The MMRM
analysis method is the convention used for regulatory filings and
discussions with regulatory authorities are in preparation.
The trial is successful in meeting the
co-primary endpoints if the significance of each endpoint is P <
0.05, or if the significance of only one co-primary endpoint is P
< 0.025. If only one primary endpoint is significant at an α
level of 0.025, then the secondary endpoint will be evaluated at
the same level of 0.025. The trial was successful, since the
differences in the least-squares mean (LSM) change from baseline to
48 weeks between the blarcamesine and placebo groups were −1.783
[95% CI, −3.314 to −0.251]; (P = 0.0226) for ADAS-Cog13, and −0.456
[95% CI, −0.831 to −0.080]; (P = 0.0175) for CDR-SB in patients
with early Alzheimer’s disease.
In addition, validated biomarkers of amyloid
beta pathology, plasma Aβ42/40 ratio increased significantly (P =
0.048), demonstrating strong anti-amyloid effects of blarcamesine
in Alzheimer’s disease patients, while MRI revealed significant
reduction in brain volume loss, including whole brain (P = 0.0005),
comparing treatment to placebo. In the respective safety
population, common treatment-emergent adverse events included
dizziness, which was transient and mostly mild to moderate in
severity, and occurred in 120 participants (35.8%) during titration
and in 76 participants (25.2%) during maintenance with blarcamesine
and 10 (6.0%) during titration and 9 (5.6%) during maintenance with
placebo.
“There is hope that new therapies for
Alzheimer’s that target the disease beyond amyloid that may slow
progression of the disease for many people with the earliest forms
of the disease,” said Marwan Noel Sabbagh, MD, Professor of
Neurology and Chairman of the Scientific Advisory Board. “The
advantage of blarcamesine (ANAVEX®2-73) is that it is a small oral
molecule that exerts clinical benefits on cognition and
neurodegeneration and could be appealing because of its route of
administration and excellent safety profile.”
This is among the first drugs to prospectively
demonstrate efficacy on biomarkers of neurodegeneration.
“These data are very exciting, particularly in a
study that can demonstrate objective slowing of markers of
neurodegeneration,” says Michael Weiner MD, Professor of Radiology
and Biomedical Imaging, Medicine, Psychiatry, and Neurology at the
University of California, San Francisco (UCSF) and Principal
Investigator of the Alzheimer's Disease Neuroimaging Initiative
(ADNI).
“Alzheimer’s disease is such a devastating
disease that affects tens of millions worldwide, and Anavex’s
clinical development is a testament to our determination to follow
the science,” said Christopher U Missling, PhD, President and Chief
Executive Officer of Anavex. “We like to thank all the people
involved in the study for their invaluable contributions and we
look forward to advancing blarcamesine as a potential new
convenient orally available treatment option for Alzheimer’s
disease.”
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 and a Phase 2b/3 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 M1 muscarinic 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 RelationsTel: 516-662-9461Email:
andrew@barwicki.com
1 Amyloid beta levels strongly correlate with abeta plaque
deposition in the brain and Alzheimer’s disease progression.2 Brain
atrophy, which is loss of brain volume is accelerated in
Alzheimer’s disease.3 Magnetic Resonance Imaging (MRI) is a
non-invasive imaging technology that produces three dimensional
detailed anatomical images.
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