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, reports preliminary 48-week open-label extension
Parkinson’s disease dementia ANAVEX®2-73-PDD-EP-001 Phase 2 study
data which demonstrated longitudinal beneficial effects of
ANAVEX®2-73 on the prespecified primary and secondary objectives,
as well as planned primary and key secondary endpoints which will
be utilized in a forthcoming pivotal study of ANAVEX®2-73 in
Parkinson’s disease.
ANAVEX®2-73 (blarcamesine) is an oral
small-molecule activator of the sigma-1 receptor (SIGMAR1), which
data suggests is pivotal to restoring neural cell homeostasis and
promoting neuroplasticity.1
Parkinson’s disease (PD) is a chronic,
debilitating CNS disease and the second largest age-related
disorder after Alzheimer’s disease.2 This study demonstrates for
the first-time that patients’ clinical symptoms consistently
improve longitudinally during the 48-week ANAVEX2-73-PDD-EP-001
Phase 2 study under active ANAVEX®2-73 treatment in Parkinson’s
disease.
The 48-week ANAVEX2-73-PDD-EP-001 (NCT04575259)
Phase 2 study assessed safety, tolerability and efficacy, measuring
among others, Movement Disorder Society-Unified Parkinson's Disease
Rating Scale (MDS-UPDRS)3 Parts I, II, III, REM Sleep Behavior
Disorder Screening Questionnaire (RBDSQ), Clinical Global
Impression – Improvement (CGI-I), as well as cognitive efficacy
endpoint Montreal Cognitive Assessment (MoCA) over a 48-week
period.
Preliminary analysis reveals that ANAVEX®2-73
(blarcamesine) was found to be generally safe and well tolerated;
and safety findings in this study are consistent with the known
safety profile of ANAVEX®2-73. In respect to efficacy, across all
efficacy endpoints, patients performed better while on
ANAVEX®2-73.
The 48-week Open Label Extension (OLE)
ANAVEX2-73-PDD-EP-001 Phase 2 study was offered to participants
after completion of the double-blind placebo-controlled
ANAVEX2-73-PDD-001 Phase 2 study. Study participants were allowed
to stay on a stable regimen of anti-Parkinson's disease medications
(including levodopa, dopamine agonists, MAO-B inhibitors, or
entacapone).
Previously, in the double-blind
ANAVEX2-73-PDD-001 Phase 2 study, ANAVEX®2-73 treatment
demonstrated statistically significant improvements compared to
placebo (ITT population) for MDS-UPDRS Total score. From baseline
to the end of the trial at 14 weeks, the MDS-UPDRS Total score
improved by -10.98 points in the ANAVEX®2-73 high dose group and
worsened by 3.53 points in the placebo group, an adjusted mean
difference of -14.51 points (p = 0.034). This corresponds to a
relative improvement of 18.9% over 14 weeks.4 This data was also
consistent with expression levels of pathological dysregulated
neurodegenerative genes, including Parkinson’s disease genes, which
were significantly restored by the therapeutic effect of
ANAVEX®2-73 (p<0.005).5
Due to the COVID-19 pandemic, the start of the
extension phase was delayed, on average, by approximately 41 weeks
at the end of the preceding double-blind placebo-controlled study
(DB). This led to a reduced enrollment rate for the extension
phase. The period between the end of the double-blind phase to the
start of the extension phase, where patients were not on
ANAVEX®2-73 treatment, is known as a ‘drug holiday’. The drug
holiday period of treatment separation provided an opportunity to
compare the trajectory of clinical scores between no ANAVEX®2-73
treatment (drug holiday) and ANAVEX®2-73 treatment in the extension
phase.
All efficacy endpoints, which includes the
MDS-UPDRS Part II + III and Clinical Global Impression –
Improvement (CGI-I) measured at the end of trial of the
double-blind study (DB EOT), the OLE Baseline, OLE Week 24, and OLE
Week 48, showed a worsening during the drug holiday. However, a
consistent improvement was observed during the extension phase when
patients resumed ANAVEX®2-73 treatment. These results are
consistent with the pattern observed for all efficacy measures in
the extension phase (see Chart and Table).6
Clinical Endpoints |
|
Change at OLE Baseline from DB EOT |
|
|
Change at Week 24 from OLE Baseline |
|
|
Change at Week 48 from OLE Baseline |
|
|
MDS-UPDRS Part III |
Mean (SE) |
4.394 (2.155) |
N=33 |
|
-2.583 (2.474) |
N=24 |
|
-3.95 (4.067) |
N=20 |
|
Median |
0 |
|
|
-0.5 |
|
|
-1 |
|
|
MDS-UPDRS Part II + III |
Mean (SE) |
6.667 (2.800) |
N=33 |
|
-3.870 (3.403) |
N=23 |
|
-2.20 (5.314) |
N=20 |
|
Median |
0 |
|
|
-1 |
|
|
-0.5 |
|
|
MDS-UPDRS Total score |
Mean (SE) |
9.818 (3.387) |
N=33 |
|
-4.739 (4.262) |
N=23 |
|
-2.25 (6.656) |
N=20 |
|
Median |
4 |
|
|
0 |
|
|
-3.5 |
|
|
RBDSQ |
Mean (SE) |
0.784 (0.439) |
N=37 |
|
-1.667 (0.424) |
N=24 |
|
-0.524 (0.620) |
N=21 |
|
Median |
0 |
|
|
-1 |
|
|
-1 |
|
|
CGI-I |
Mean (SE) |
0.629 (0.184) |
N=35 |
|
-0.542 (0.295) |
N=24 |
|
-0.7 (0.309) |
N=20 |
|
Median |
0 |
|
|
0 |
|
|
-1 |
|
|
MoCA |
Mean (SE) |
-1.45455 (0.433) |
N=33 |
|
-0.2912 (0.519) |
N=24 |
|
-1.2 (0.537) |
N=20 |
|
Median |
-1 |
|
|
0 |
|
|
-0.5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
OLE = Open Label
Extension study; DB = Double-Blind study; EOT = End of Trial |
|
|
The calculations were
done with all available data at reference time points |
|
|
These results should
be interpreted cautiously due to the nature of the study and the
small sample sizes |
MDS-UPDRS = Movement
Disorder Society-Unified Parkinson Disease Rating Scale |
|
|
RBDSQ = REM Sleep Behavior Disorder Screening Questionnaire |
|
|
|
|
CGI-I = Clinical Global Impression – Improvement |
|
|
|
|
|
MoCA = Montreal
Cognitive Assessment (cognitive decline slowing in OLE) |
|
|
Except for MoCA,
Positive scores respresent decline; Negative scores represent
improvement |
The two endpoints, MDS-UPDRS Part II + III and Clinical Global
Impression – Improvement (CGI-I) measured in this study are the
planned primary and key secondary endpoints in Anavex’s forthcoming
pivotal 6-month Parkinson’s disease study.
“It is encouraging that the patients’ clinical
symptoms consistently improved longitudinally over time during the
extension phase under active ANAVEX®2-73 treatment,” said
Christopher U Missling, PhD, President & CEO of Anavex. “This
data suggests ANAVEX®2-73’s potential capability to slow and
potentially reverse the life altering symptoms of Parkinson’s
disease, an urgent unmet global need.”
Moreover, at the request of the participants
completing the 48-week open-label extension study, patient
requested treatment with ANAVEX®2-73 is continuing beyond the
open-label 48-weeks through the compassionate use Special Access
Scheme. Currently, participants in the compassionate use program
for ANAVEX®2-73 have been on average, for over 2 years and
counting.
The Michael J. Fox Foundation (MJFF) awarded
Anavex a research grant for an imaging-focused Parkinson’s disease
clinical trial with ANAVEX®2-73.7 MJFF previously awarded Anavex a
research grant, which fully funded a preclinical study that
established ANAVEX®2-73 as a potentially disease-modifying
treatment for Parkinson’s disease.8
Anavex Life Sciences’ therapeutic product
platform includes orally available small molecule lead drug
candidate ANAVEX®2-73 for the treatment of Alzheimer’s disease,
Parkinson’s disease and Rett syndrome and ANAVEX®3-71 for
schizophrenia, Alzheimer’s disease, and frontotemporal
dementia.
About Parkinson’s Disease (PD)
Parkinson’s disease is a chronic and progressive
neurological disorder that is characterized by well-known motor
symptoms including tremors, stiffness of limbs, slowness of
movements, and difficulties with posture and balance, as well as by
non-motor symptoms. It is the second most common neurological
disorder and approximately one million people in the United States,
and more that 10 million people worldwide, live with this disease.
Parkinson’s disease is more common in people over 60 years of age
and its prevalence is expected to increase significantly as the
average age of the population increases. Current Parkinson’s
treatments are only effective in managing symptoms of the disease,
mainly through the use of levodopa and dopamine agonists. As the
disease progresses and dopaminergic neurons continue to be lost,
these drugs eventually become less effective at treating the
symptoms.
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 recently 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 Advances in Experimental Medicine and Biology Volume 964
(2017) Sigma Receptors: Their Role in Disease and as Therapeutic
Targets.2 Reeve A, Simcox E, Turnbull D. Ageing and Parkinson's
disease: why is advancing age the biggest risk factor? Ageing Res
Rev. 2014 Mar;14(100):19-30. doi: 10.1016/j.arr.2014.01.004. Epub
2014 Feb 3. PMID: 24503004; PMCID: PMC3989046; Mhyre TR, Boyd JT,
Hamill RW, Maguire-Zeiss KA. Parkinson's disease. Subcell Biochem.
2012;65:389-455. doi: 10.1007/978-94-007-5416-4_16. PMID: 23225012;
PMCID: PMC4372387.3 The Movement Disorder Society-Unified Parkinson
Disease Rating Scale (MDS-UPDRS) is a commonly used tool to measure
Parkinson disease (PD) progression.4
https://www.anavex.com/post/anavex-life-sciences-announces-presentation-of-phase-2-clinical-biomarker-data-from-pdd-study5
https://www.anavex.com/post/anavex-announces-first-entire-clinical-alzheimer-s-gene-pathway-data-of-anavex-2-73-at-aaic-20226
The observed worsening (increase) of MDS-UPDRS scores in this study
during drug holiday is consistent with the literature, e.g.: Holden
SK, Finseth T, Sillau SH, Berman BD. Progression of MDS-UPDRS
Scores Over Five Years in De Novo Parkinson Disease from the
Parkinson's Progression Markers Initiative Cohort. Mov Disord Clin
Pract. 2018 Jan-Feb;5(1):47-53. doi: 10.1002/mdc3.12553. Epub 2017
Sep 22; Simuni T, Siderowf A, Lasch S, Coffey CS, Caspell-Garcia C,
Jennings D, Tanner CM, Trojanowski JQ, Shaw LM, Seibyl J, Schuff N,
Singleton A, Kieburtz K, Toga AW, Mollenhauer B, Galasko D, Chahine
LM, Weintraub D, Foroud T, Tosun D, Poston K, Arnedo V, Frasier M,
Sherer T, Chowdhury S, Marek K; Parkinson's Progression Marker
Initiative*. Longitudinal Change of Clinical and Biological
Measures in Early Parkinson's Disease: Parkinson's Progression
Markers Initiative Cohort. Mov Disord. 2018 May;33(5):771-782. doi:
10.1002/mds.27361.7
https://www.anavex.com/anavex-life-sciences-receives-michael-j-fox-foundation-grant-for-clinical-study-of-anavex2-73-blarcamesine-in-people-with-parkinsons-disease/8
https://www.anavex.com/parkinsons-disease-data-mjf-conference/;
https://www.anavex.com/anavex-awarded-grant-from-the-michael-j-fox-foundation-for-parkinsons-research/
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/e1fa7f1d-3edc-495d-a6ab-11b65c4923af
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