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 reported that ANAVEX®2-73 (blarcamesine) is
featured in a recent peer-reviewed publication in the journal of
Neuropharmacology, titled “Future avenues for Alzheimer’s disease
detection and therapy: liquid biopsy, intracellular signaling
modulation, systems pharmacology drug discovery” from the series of
the special issue on ’The Quest for Disease-Modifying Therapies for
Neurodegenerative Disorders’.1
The authors of the paper describe gene
biomarkers associated improved drug response with consistent
results across the different measurements of both cognition and
activities of daily living and function with ANAVEX®2-73, a
selective SIGMAR1 agonist, observed in a 57-week
multicenter Phase 2a open-label adaptive design clinical trial
(ANAVEX2-73-002) of 32 mild-to-moderate Alzheimer’s disease
patients (aged 55–85). They declare that Alzheimer’s disease
patients with fully operational SIGMAR1 gene show improved benefits
with ANAVEX®2-73, whereas those carrying gene variants have a
limited benefit. Since the majority of the population, around 80%,
has a totally functional SIGMAR1 gene, most of patients are
supposed to benefit from ANAVEX®2-73.
They further state that SIGMAR1 stimulation
prevents Aβ-induced neurotoxicity and moreover, that SIGMAR1
activation is associated with a significant slow-down of
Alzheimer’s disease-related excitotoxicity, thus promoting synaptic
remodeling with improved plasticity. In addition, the
biomarker-driven clinical data is described, thus, enabling
targeted therapy and a precision medicine-guided approach. PET scan
data previously confirmed dose-dependent target engagement of
SIGMAR1 with ANAVEX®2-73.2
The precision medicine knowledge from this study
was incorporated into the design of the currently ongoing and
presently over 86%-enrolled placebo-controlled 450-patient Phase
2b/3 ANAVEX®2-73 clinical study in Alzheimer's disease including
the above characterized SIGMAR1 gene as prespecified endpoints and
utilizing differentiated patient selection criteria using ADAS-Cog
(cognition) and ADCS-ADL (activities of daily living and function)
as primary endpoints.3
The Neuropharmacology publication noted that in
the clinical study, 57 weeks of oral once daily ANAVEX®2-73
treatment showed patients improved cognition scores by +2.0 points
on MMSE, a 9% mean improvement from baseline to 57 weeks,
corresponding to a calculated ADAS-Cog score change of -3.4
(improvement). In these same patients ANAVEX®2-73 also improved
ADCS-ADL, by +4.9 points, a 7% mean improvement from baseline to 57
weeks.
An extension of the published study
(ANAVEX2-73-003) demonstrated that for the same patients at week 70
MMSE scores improved by +3.0, a 14% improvement from baseline,
corresponding to a calculated ADAS-Cog score change of -5.1
(improvement). In these same patients, ANAVEX®2-73 also improved
ADCS-ADL, by +6.0 points, an 8% mean improvement from baseline to
70 weeks. The mean MMSE and ADCS-ADL baseline scores for these
patients in this study were 22.3 and 71.1, respectively.4,5
This data seems to be consistent with the effect
of ANAVEX®2-73 on cognition assessed in the recently completed
placebo-controlled Phase 2 study of 132 patients with Parkinson’s
disease dementia (ANAVEX2-73-PDD-001) with once-daily
administration of oral 30 mg ANAVEX®2-73, 50 mg ANAVEX®2-73 and
placebo for 14 weeks. The observed statistically significant
improvement of CDR system Episodic Memory of +42.22 between 50 mg
ANAVEX®2-73 and placebo was also dose-dependent (p = 0.003).6 CDR
system Episodic Memory has been shown to be highly correlated (70%)
with the ADAS-Cog score (r = 0.7).7 The calculated
corresponding ADAS-Cog mean change from baseline score is -1.9
(improvement) for patients in the 50 mg dose group, an 8% mean
improvement from baseline to 14 weeks. The difference between the
ANAVEX®2-73 group and the placebo group in the change from baseline
at 14 weeks was a 4.0-point improvement of calculated corresponding
ADAS-Cog score (p = 0.015).
The Mini-Mental State Exam (MMSE) and the
ADAS-Cog (Alzheimer's Disease Assessment Scale–Cognitive Subscale)
are standard tests for assessing changes in cognition in
Alzheimer’s disease trials and known to correlate to a high
degree.8 The ADCS-ADL (Alzheimer’s Disease Cooperative
Study–Activities of Daily Living), assesses the competence of
patients with Alzheimer’s disease in basic and instrumental
function or activities of daily living.
Alzheimer’s is a progressive disease and over
time, a patient’s cognition will always worsen. “Experience based
on longitudinal studies of ambulatory patients with mild to
moderate Alzheimer’s disease suggest that scores on the ADAS-cog
worsen by 6-12 points per year” with the annualized rate of decline
might be smaller depending on the disease stage, according to FDA’s
Prescription Information sheet for ARICEPT® (donepezil), a drug
approved for the treatment of dementia of the Alzheimer’s
type.9
While the placebo-controlled 450-patient Phase
2b/3 ANAVEX®2-73 clinical study in Alzheimer's disease is currently
ongoing, prior clinical research in Alzheimer’s disease conducted
by other sponsors can serve as a contextual reference for estimates
of an expected rate of decline in cognition (MMSE and ADAS-Cog) and
function (ADCS-ADL) in placebo patients:
-
In 2019, a randomized controlled trial of aducanumab (Biogen) was
conducted in >1,000 patients with early Alzheimer’s disease.10
In this Phase 3 study (EMERGE), patients on placebo showed from
baseline to week 50 a mean decline in cognition of approximately
-2.2 points on MMSE, an 8.3% decline, and from baseline to week 78
approximately -3.3 points on MMSE, a 12.5% decline, respectively.
Mean baseline MMSE score was 26.4.
-
Large placebo arm data from 20 randomized controlled clinical
trials including over 4500 mild-to-moderate Alzheimer’s disease
patients treated with standard of care, containing ARICEPT®
(donepezil, Eisai) and memantine was analyzed.11 In this analysis,
patients on placebo showed from baseline to week 52 a mean decline
in cognition of approximately -2.05 points on MMSE, a 10% decline
and from baseline to week 78 approximately -3.4 points on MMSE, a
16% decline, respectively, with a calculated mean baseline MMSE
score of 21.0. The respective ADAS-Cog decline was 3.9 points from
baseline to week 52 and a decline of 6.6 points from baseline to
week 78, respectively.
-
A randomized controlled study including of ARICEPT® (donepezil,
Eisai) and memantine was conducted in >500 patients in the
placebo arm with mild-to-moderate Alzheimer’s disease.12 In this
Phase 3 study, patients on placebo showed from baseline to week 76
an estimated mean decline in cognition of approximately -3.4 points
on MMSE, a 16% decline from baseline. Mean baseline MMSE score was
20.9. The mean ADAS-Cog decline was 6.4 points from baseline to
week 76. The mean ADCS-ADL decline was -9.0 points from baseline to
week 76.
ANAVEX®2-73 is currently in a late-stage Phase
2b/3 Alzheimer's disease clinical trial utilizing same dosing
regimen as in the above-described completed Parkinson’s disease
dementia (ANAVEX2-73-PDD-001) study with differentiated patient
selection criteria.13
“This paper highlights the relevance of the
analyses of gene expression data in precision medicine to drug
development that may predict increased chances of success of
Alzheimer’s disease treatments, which is especially relevant in
late-stage clinical studies like the ongoing ANAVEX®2-73 Phase 2b/3
clinical Alzheimer's disease study,” said Christopher U Missling,
PhD, President and Chief Executive Officer of Anavex.
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.14
Anavex Life Sciences’ product portfolio includes
small molecule drug lead candidate ANAVEX®2-73 for the treatment of
Alzheimer’s disease, Parkinson’s disease and Rett syndrome.
About Alzheimer’s Disease
Alzheimer’s disease is a progressive
degenerative brain disorder that gradually destroys a person's
memory and ability to learn, reason, make judgments, communicate
and carry out daily activities. An estimated 5.7 million Americans
have currently Alzheimer's dementia. Alzheimer’s is the most common
cause of dementia among older adults and is estimated to rank as
the third leading cause of death for older people in the United
States, just behind heart disease and cancer. In 2020, Alzheimer's
and other dementias cost the nation $305 billion. By 2050, these
costs could rise as high as $1.1 trillion.15 There are currently
over 50 million people living with dementia around the world, with
numbers expected to increase to nearly 152 million by 2050.16
Almost 10 million new cases of dementia are diagnosed each year
worldwide, implying one new case every 3 seconds, and a significant
increase in the caregiving burden placed on society and
families.17
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),
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 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 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 Hampel H, Vergallo A, Caraci F, Cuello AC, Lemercier P, Vellas
B, Giudici KV, Baldacci F, Hänisch B, Haberkamp M, Broich K,
Nisticò R, Emanuele E, Llavero F, Zugaza JL, Lucía A, Giacobini E,
Lista S; Alzheimer Precision Medicine Initiative. Future avenues
for Alzheimer's disease detection and therapy: liquid biopsy,
intracellular signaling modulation, systems pharmacology drug
discovery. Neuropharmacology. 2021 Mar 1;185:108081. doi:
10.1016/j.neuropharm.2020.108081. Epub 2020 May 11. PMID:
32407924.2 https://assets.researchsquare.com/files/rs-189177/v1/65385792-095a-4505-90c4-c0b85c76dbd1.pdf.3
ClinicalTrials.gov Identifier: NCT03790709.4 Hampel H. et al.,
2018. Full genomic analysis of ANAVEX®2-73 phase 2a Alzheimer’s
disease study identifies biomarkers enabling targeted therapy and a
precision medicine approach. Alzheimer’s & Dementia 14,
P1519–P1520. https://doi.org/10.1016/j.jalz.2018.07.027.5 Hampel H.
et al. (2020). A precision medicine framework using artificial
intelligence for the identification and confirmation of genomic
biomarkers of response to an Alzheimer's disease therapy: Analysis
of the blarcamesine (ANAVEX2‐73) Phase 2a clinical study.
Alzheimer's & Dementia: Translational Research & Clinical
Interventions, 6(1),
e12013.6 https://www.anavex.com/proof-of-concept-controlled-phase-2-clinical-trial-data-evaluating-anavex2-73-blarcamesine-in-parkinsons-disease-dementia-presented-at-ctad-2020-conference/.7
Wesnes K. et al., Computerized cognition assessment during
acetylcholinesterase inhibitor treatment in Alzheimer’s disease.
Acta Neurol Scand 2010; 122:270–7.8 Solomon T.M. et al.,
Correlational analysis of 5 commonly used measures of cognitive
functioning and mental status: an update. Am J Alzheimers Dis Other
Demen. 2014
Dec;29(8):718-22.9 https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020690s042,021720s014,022568s011lbl.pdf
(2018).10 Source: Biogen, EMERGE Phase III study, slide
24, https://investors.biogen.com/static-files/8e58afa4-ba37-4250-9a78-2ecfb63b1dcb
(2020).11 Thomas RG, Albert M, Petersen RC, Aisen PS. Longitudinal
decline in mild-to-moderate Alzheimer’s disease: Analyses of
placebo data from clinical trials. Alz & Dem 2016; 12:
598-60312 Doody RS et al. (2013) N Engl J Med; 369:341-35013
ClinicalTrials.gov Identifier: NCT0379070914 Advances in
Experimental Medicine and Biology Volume 964 (2017) Sigma
Receptors: Their Role in Disease and as Therapeutic Targets.15
https://www.nia.nih.gov/health/alzheimers;
https://www.alz.org/alzheimers-dementia/facts-figures;16
Alzheimer's Disease International. World Alzheimer Report 2019.
https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf.17
AARP. 2020 Report: Caregiving in the U.S.
https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001.pdf.
Anavex Life Sciences (NASDAQ:AVXL)
Historical Stock Chart
From Aug 2024 to Sep 2024
Anavex Life Sciences (NASDAQ:AVXL)
Historical Stock Chart
From Sep 2023 to Sep 2024