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) disorders, today reported top-line results from a U.S. Phase
2 randomized, double-blind, placebo-controlled trial of ANAVEX®2-73
(blarcamesine) in adult female patients with Rett syndrome.
The primary endpoint of the trial was safety.
The convenient oral liquid once-daily dosing of 5 mg ANAVEX®2-73
was well-tolerated and demonstrated dose-proportional PK
(pharmacokinetics). Adverse events related to study drug were
similar between ANAVEX®2-73 (13.3%) and placebo (10%), with no
reported serious adverse events (SAEs). The safety profile of
ANAVEX®2-73 in this trial is consistent with prior clinical trial
data.
All secondary efficacy endpoints of the trial
showed statistically significant and clinically meaningful
sustained improvements for ANAVEX®2-73 compared to placebo,
consisting of the Rett Syndrome Behaviour Questionnaire (RSBQ) (p =
0.048) and the Clinical Global Impression Improvement Scale (CGI-I)
score (p = 0.014) in the intent-to-treat (ITT) population (n = 25).
Statistically significant differences in patient symptoms between
the active and placebo groups occurred as early as 4 weeks
following the initiation of ANAVEX®2-73 administration.
Improvements in RSBQ Total scores were correlated with parallel
decreases (improvements) in glutamate plasma levels.
ANAVEX®2-73 activates the sigma-1 receptor
(SIGMAR1). Data suggests that activation of the sigma-1 receptor
(SIGMAR1) is pivotal to restoring neural cell homeostasis and
promoting neuroplasticity.1 Consistent with previous ANAVEX®2-73
clinical trials, patients carrying the common form of the SIGMAR1
gene treated with ANAVEX®2-73 experienced stronger improvements in
the prespecified efficacy endpoints.
All twenty-five patients in this randomized
study elected to enter a 12-week ANAVEX®2-73 extension study.
Anavex will be advancing its Expanded Access Policy in order to
provide long-term therapy to current participants with Rett
syndrome under an expanded access program for ANAVEX®2-73.
“The outcome of this trial is very promising in
terms of both safety and clinical improvement. Despite the
challenges of the older age of the cohort (patients were over 18
years of age) and the relatively low dose (5 mg daily), ANAVEX®2-73
demonstrated clinically meaningful improvements in outcome measures
evaluating multiple impairments,” commented Walter E Kaufmann, MD,
Principal Investigator. Subsequent to his appointment as Principal
Investigator of this Phase 2 ANAVEX®2-73 trial in adult Rett
syndrome patients, Dr. Kaufmann joined Anavex as Chief Medical
Officer. He also said, “Moreover, the convergent clinical evidence
was supported by parallel changes in a key biomarker of disease.
This strong body of data opens the possibility of successful
treatment for both adults and children with Rett syndrome and early
interventions for modifying the course of the disease.”
Based on the results in this first of its kind
U.S. Phase 2 (ANAVEX®2-73-RS-001)2 study in adult patients with
Rett syndrome, Anavex is planning to meet with FDA to discuss the
approval pathway. There are no FDA-approved drugs for Rett
syndrome. ANAVEX®2-73 has Fast Track designation, Rare Pediatric
Disease designation and Orphan Drug designation from the FDA for
the treatment of Rett syndrome and may be considered for
accelerated approval.
ANAVEX®2-73 is currently being evaluated for
Rett syndrome in two other ongoing placebo-controlled clinical
studies: The Phase 2 AVATAR trial in adult Rett syndrome
(ANAVEX®2-73-RS-002)3 and the EXCELLENCE Phase 2/3 pediatric Rett
syndrome study (ANAVEX®2-73-RS-003)4.
“These are strong and consistent data
demonstrating tolerability and rapid and clinically meaningful
improvements in key measures of Rett syndrome symptoms in the
ANAVEX®2-73 treatment group compared to placebo,” said Christopher
U Missling, PhD, President & Chief Executive Officer of Anavex.
I would like to thank the patients and caregivers who participated
in this trial, the Anavex team, trial clinics, and doctors who have
worked tirelessly on this program. Special thanks go to the
Rettsyndrome.org Foundation, which provided financial support for
this trial; we look forward to continuing the journey
together."
Summary of Top-line ANAVEX®2-73
(blarcamesine) Placebo-Controlled Phase 2 U.S. Rett Syndrome Trial
Results
The study evaluated the safety, pharmacokinetics
and efficacy of ANAVEX®2-73 in 25 adult female patients diagnosed
with Rett syndrome (positive MECP2 gene mutation).
Effect on Rett Syndrome Symptoms:
- ANAVEX®2-73 treatment yielded a
statistically significant, drug exposure-dependent response in the
RSBQ Total scores, when compared to placebo, in the ITT cohort (all
participants, p = 0.048).
- 66.7% of ANAVEX®2-73 treated
subjects showed a statistically significant improvement in drug
exposure-dependent RSBQ response as compared to 10% of the subjects
on placebo in the ITT cohort (all participants, p = 0.011).
- Improvements in this adult
population with Rett syndrome, assessed by RSBQ Total scores, are
considered clinically meaningful according to published criteria
applied to neurodevelopmental disorders.5
- ANAVEX®2-73 treatment resulted in a
sustained improvement in CGI-I scores throughout the 7-week study,
when compared to placebo in the ITT cohort (all participants, p =
0.014).
- 86.7% of ANAVEX®2-73 treated
subjects showed a statistically significant CGI-I response, defined
as sustained improvement to treatment, as compared to 40% of the
subjects on placebo in the ITT cohort (all participants, p =
0.014).
Safety and Tolerability:
- ANAVEX®2-73 was found to be well tolerated with very good
medication compliance during the trial.
- All 25 subjects completed the
study. The overall incidence of patients who experienced adverse
events related to study drug, which were mild, or moderate was
13.3% (2) for the ANAVEX®2-73 treatment group and 10% (1) for the
placebo group.No serious treatment emergent adverse events were
reported during the course of the trial.
- There were no clinically significant differences in vital
signs, lab values and EKG parameters between the active drug and
placebo groups.
- Collectively, the study results are consistent with the known
safety profile of ANAVEX®2-73.
- There was no signal for increased risk for common
disorder-related manifestations.
About Rett Syndrome
Rett syndrome is a devastating, non-inherited
genetic post-natal progressive neurodevelopmental disorder that
occurs almost exclusively in girls and leads to severe impairments,
affecting nearly every aspect of the child’s life: their ability to
speak, walk, eat and easily breathe. The hallmark of Rett syndrome
is near constant repetitive hand movements while awake. The disease
is characterized by normal early growth and development (6 to 18
months) followed by a slowing of development, loss of purposeful
use of the hands, distinctive hand movements, autistic features,
slowed brain and head growth, ataxia, seizures and intellectual
disability.Rett syndrome is caused by mutations in the MECP2 gene
and strikes all racial and ethnic groups. The disease occurs
worldwide in approximately one in every 10,000 to 15,000 live
births. The population of patients with Rett syndrome is estimated
to be between 6,000 to 9,000 patients in the U.S. There is
currently no cure for Rett syndrome.
About ANAVEX®2-73-RS-001 Clinical Study
(NCT03758924)
The Phase 2 trial is a randomized double-blind,
placebo-controlled safety, tolerability, pharmacokinetic and
efficacy study of oral liquid ANAVEX®2-73 to treat Rett syndrome in
a total of 31 adult patients with Rett syndrome over a 7-weeks
treatment period were evaluated incorporating precision medicine
biomarkers. Preceding the placebo-controlled randomization of 25
patients (Part B), a 6-patient cohort (Part A) underwent a 7-weeks
pharmacokinetic (PK) assessment with safety, tolerability,
pharmacokinetic and efficacy evaluation of ANAVEX®2-73. All
patients who participated in the study were eligible to receive
ANAVEX®2-73 under an open label extension protocol.
About Rettsyndrome.org
Rettsyndrome.org is the most comprehensive
nonprofit organization dedicated to accelerating research of
treatments and a cure for Rett syndrome and related disorders while
providing information and family empowerment. As the world’s
leading private funder of Rett syndrome research, Rettsyndrome.org
has funded over $40M in high-quality, peer-reviewed research grants
and programs to date. The organization hosts the largest global
gathering of Rett researchers and clinicians to establish research
direction for the future. Rettsyndrome.org, a 501(c)(3)
organization, has earned Charity Navigator’s most prestigious 4
star rating year after year. To learn more about our work and Rett
syndrome, visit www.rettsyndrome.org or call (800) 818-7388
(RETT).
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a
publicly traded biopharmaceutical company dedicated to the
development of 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, pain and various types of
cancer. Anavex’s lead drug candidate, ANAVEX®2-73, recently
completed successfully a Phase 2a clinical trials for Alzheimer’s
disease and a Phase 2 proof-of-concept study in Parkinson’s disease
dementia. 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
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 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:Clint TomlinsonEmail:
ir@anavex.com
Media:Melyssa WeibleElixir
Health Public Relations201-723-5805mweible@elixirhealthpr.com
_______________________
1 Advances in Experimental Medicine and Biology
Volume 964 (2017) Sigma Receptors: Their Role in Disease and as
Therapeutic Targets.2 ClinicalTrials.gov Identifier: NCT037589243
ClinicalTrials.gov Identifier: NCT039414444 ClinicalTrials.gov
Identifier: NCT043044825 Chatham et al. Adaptive behavior in
autism: Minimal clinically important differences on the
Vineland-II. Autism Res. 2018;11(2):270-283. doi:10.1002/aur.1874;
Luu et al. Response to Placebo in Fragile X Syndrome Clinical
Trials: An Initial Analysis. Brain Sci. 2020 Sep 11;10(9):629. doi:
10.3390/brainsci10090629
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