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 predictive biomarker of response
established with SIGMAR1 mRNA expression correlates significantly
with responses in primary clinical efficacy endpoints from the U.S.
Phase 2 randomized, double-blind, placebo-controlled trial of
ANAVEX®2-73 (blarcamesine) in adult female patients with Rett
syndrome.
ANAVEX®2-73 activates the sigma-1 receptor
(SIGMAR1). Data suggests that activation of SIGMAR1 results in the
restoration of complete housekeeping function within the body and
is pivotal to restoring neural cell homeostasis and promoting
neuroplasticity.1 Recent independent findings strengthen the
understanding of the beneficial effect of SIGMAR1 activation as
compensatory mechanism to chronic CNS diseases.2
Rett syndrome is a chronic CNS disease caused by
a spontaneous mutation of one gene, MECP2. This study demonstrates
for the first-time that a biomarker correlates with clinical
efficacy in Rett syndrome. ANAVEX®2-73 treatment resulted in
increases in the mRNA expression of SIGMAR1, the gene coding for
the receptor targeted by ANAVEX®2-73, which correlated with
clinical efficacy as measured by both primary efficacy endpoints
(ITT population), namely RSBQ (p = 0.035) and CGI-I (p =
0.029).
In addition, prespecified patients with WT
SIGMAR1 in the clinical trial demonstrated a clinically meaningful
and statistically significant 14.5-point (p = 0.009) improvement
over placebo in the RSBQ total score, the trial’s key efficacy
endpoint. This magnitude of the improvement with ANAVEX®2-73
compares favorably to published data currently in clinical
development, which reported an average difference of 4.4 points in
RSBQ total score versus placebo, despite an advantage of higher
dose and lower age compared to ANAVEX®2-73-RS-001 trial.3The RSBQ
demonstrated balanced improvements across all the instrument’s
subscales during the trial period of 7 weeks, including general
mood, breathing, hand behavior, repetitive face movements, body
rocking, night-time behavior, fear/anxiety, walking/standing.
The Anxiety, Depression, and Mood Scale (ADAMS),
which is a measure of anxiety and mood symptoms in individuals with
intellectual disability,4 has been clinically validated for use in
Rett syndrome5 and in Fragile X syndrome,6 demonstrated clinically
meaningful and statistically significant 12.9-point (p = 0.005)
improvement for ANAVEX®2-73 treated adult patients with Rett
syndrome vs placebo in prespecified patients with WT SIGMAR1.The
ADAMS also demonstrated balanced improvements across all different
subscales during the trial period of 7 weeks, including
manic/hyperactive behavior, depressed mood, social avoidance,
general anxiety, obsessive compulsive behavior.
“The biomarker-driven clinical evidence is very
exciting and opens the possibility of successful treatment for both
adults and children with Rett syndrome and early interventions for
modifying the course of the disease,” commented Walter E. Kaufmann,
MD, Principal Investigator and Chief Medical Officer of Anavex.
“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 on average 24 years of age)
and the relatively low dose (5 mg daily), ANAVEX®2-73 demonstrated
clinically meaningful improvements in outcome measures evaluating
multiple impairments, which are supported by correlations with
objective biomarkers.”
With this convincing biomarker correlating
efficacy data of U.S. Phase 2 (ANAVEX®2-73-RS-001)7 study in adult
patients with Rett syndrome, Anavex is planning to meet with the
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. The study was supported by the
Rettsyndrome.org Foundation.
ANAVEX®2-73 is currently being evaluated for
Rett syndrome in two other ongoing late-stage placebo-controlled
clinical studies: The AVATAR trial in adult Rett syndrome
(ANAVEX®2-73-RS-002)8 and the EXCELLENCE pediatric Rett syndrome
trial (ANAVEX®2-73-RS-003)9.
“These are strong and consistent data
demonstrating biomarker-correlated 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. “Our team is dedicated to provide for this urgent unmet
need of patients with Rett syndrome, and we believe our ANAVEX®2-73
Rett syndrome program sets us on a course to potentially offer a
new, unique and mechanistically differentiated treatment option
also for other diseases associated with autism spectrum
disorder.”
Anavex Life Sciences’ product portfolio platform
includes small molecule drug lead candidate ANAVEX®2-73 for the
treatment of Alzheimer’s disease, Parkinson’s disease and Rett
syndrome and ANAVEX®3-71 for frontotemporal dementia.
Six photos accompanying this announcement are
available
at: https://www.globenewswire.com/NewsRoom/AttachmentNg/458cacc7-b626-4c8e-ac48-1582932f076e
https://www.globenewswire.com/NewsRoom/AttachmentNg/e9b29318-7433-4f0c-8d86-6bab9041fa3f
https://www.globenewswire.com/NewsRoom/AttachmentNg/d8f3ccaf-25a9-474d-9ab7-1698aad08f32
https://www.globenewswire.com/NewsRoom/AttachmentNg/9dfd788d-8d4c-423f-9d31-135dcd32c23a
https://www.globenewswire.com/NewsRoom/AttachmentNg/50520407-00a5-4191-95af-70e2bc534a73
https://www.globenewswire.com/NewsRoom/AttachmentNg/437f14f0-b253-46d6-a5dd-aeeed6efc544
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 approximately 11,000 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 (End of Trial, EOT) 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.
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.
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 (blarcamesine),
successfully completed a Phase 2a clinical trial for Alzheimer’s
disease and recently a Phase 2 proof-of-concept study in
Parkinson’s disease dementia and a Phase 2 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 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 Advances in Experimental Medicine and Biology Volume 964
(2017) Sigma Receptors: Their Role in Disease and as Therapeutic
Targets.2 Prasanth MI, Malar DS, Tencomnao T, Brimson JM. The
emerging role of the sigma-1 receptor in autophagy: Hand-in-hand
targets for the treatment of Alzheimer's. Expert Opin Ther Targets.
2021 Jun 10. doi: 10.1080/14728222.2021.1939681. Epub ahead of
print. PMID: 34110944.3 Glaze DG, Neul JL, Kaufmann WE,
Berry-Kravis E, Condon S, Stoms G, Oosterholt S, Della Pasqua O,
Glass L, Jones NE, Percy AK; Rett 002 Study Group. Double-blind,
randomized, placebo-controlled study of trofinetide in pediatric
Rett syndrome. Neurology. 2019 Apr 16;92(16):e1912-e1925. doi:
10.1212/WNL.0000000000007316. Epub 2019 Mar 27. PMID: 30918097;
PMCID: PMC6550498.4 Esbensen AJ, Rojahn J, Aman MG, Ruedrich S.
Reliability and validity of an assessment instrument for anxiety,
depression, and mood among individuals with mental retardation. J
Autism Dev Disord. 2003;33:617–29 Kluwer Academic Publishers-Plenum
Publishers.5 Barnes KV, Coughlin FR, O'Leary HM, Bruck N, Bazin GA,
Beinecke EB, Walco AC, Cantwell NG, Kaufmann WE. Anxiety-like
behavior in Rett syndrome: characteristics and assessment by
anxiety scales. J Neurodev Disord. 2015;7(1):30. doi:
10.1186/s11689-015-9127-4. Epub 2015 Sep 15.6 Cordeiro L, Ballinger
E, Hagerman R, Hessl D. Clinical assessment of DSM-IV anxiety
disorders in fragile X syndrome: prevalence and characterization. J
Neurodev Disord. 2011;3:57–67. doi: 10.1007/s11689-010-9067-y. Epub
2010 Dec 3.7 ClinicalTrials.gov Identifier: NCT037589248
ClinicalTrials.gov Identifier: NCT039414449 ClinicalTrials.gov
Identifier: NCT04304482
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