NEW YORK, March 16, 2021 (GLOBE NEWSWIRE) — Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical firm creating differentiated therapeutics for the therapy of neurodegenerative and neurodevelopmental problems together with Alzheimer’s illness, Parkinson’s illness, Rett syndrome and different central nervous system (CNS) ailments, immediately reported that ANAVEX®2-73 (blarcamesine) is featured in a current peer-reviewed publication in the journal of Neuropharmacology, titled “Future avenues for Alzheimer’s illness detection and remedy: liquid biopsy, intracellular signaling modulation, techniques pharmacology drug discovery” from the sequence of the particular concern on ’The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders’.1
The authors of the paper describe gene biomarkers related improved drug response with constant outcomes throughout the completely different measurements of each cognition and actions of day by day dwelling and perform with ANAVEX®2-73, a selective SIGMAR1 agonist, noticed in a 57-week multicenter Phase 2a open-label adaptive design scientific trial (ANAVEX2-73-002) of 32 mild-to-moderate Alzheimer’s illness sufferers (aged 55–85). They declare that Alzheimer’s illness sufferers with absolutely operational SIGMAR1 gene present improved advantages with ANAVEX®2-73, whereas these carrying gene variants have a restricted profit. Since nearly all of the inhabitants, round 80%, has a completely useful SIGMAR1 gene, most of sufferers are supposed to profit from ANAVEX®2-73.
They additional state that SIGMAR1 stimulation prevents Aβ-induced neurotoxicity and furthermore, that SIGMAR1 activation is related to a important slow-down of Alzheimer’s disease-related excitotoxicity, thus selling synaptic transforming with improved plasticity. In addition, the biomarker-driven scientific information is described, thus, enabling focused remedy and a precision medicine-guided method. PET scan information beforehand confirmed dose-dependent goal engagement of SIGMAR1 with ANAVEX®2-73.2
The precision drugs data from this research was integrated into the design of the at present ongoing and presently over 86%-enrolled placebo-controlled 450-patient Phase 2b/3 ANAVEX®2-73 scientific research in Alzheimer’s illness together with the above characterised SIGMAR1 gene as prespecified endpoints and using differentiated affected person choice standards utilizing ADAS-Cog (cognition) and ADCS-ADL (actions of day by day dwelling and perform) as major endpoints.3
The Neuropharmacology publication famous that in the scientific research, 57 weeks of oral as soon as day by day ANAVEX®2-73 therapy confirmed sufferers improved cognition scores by +2.0 factors on MMSE, a 9% imply enchancment from baseline to 57 weeks, akin to a calculated ADAS-Cog rating change of -3.4 (enchancment). In these identical sufferers ANAVEX®2-73 additionally improved ADCS-ADL, by +4.9 factors, a 7% imply enchancment from baseline to 57 weeks.
An extension of the revealed research (ANAVEX2-73-003) demonstrated that for the identical sufferers at week 70 MMSE scores improved by +3.0, a 14% enchancment from baseline, akin to a calculated ADAS-Cog rating change of -5.1 (enchancment). In these identical sufferers, ANAVEX®2-73 additionally improved ADCS-ADL, by +6.0 factors, an 8% imply enchancment from baseline to 70 weeks. The imply MMSE and ADCS-ADL baseline scores for these sufferers in this research had been 22.3 and 71.1, respectively.4,5
This information appears to be according to the impact of ANAVEX®2-73 on cognition assessed in the lately accomplished placebo-controlled Phase 2 research of 132 sufferers with Parkinson’s illness 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 noticed statistically important enchancment of CDR system Episodic Memory of +42.22 between 50 mg ANAVEX®2-73 and placebo was additionally dose-dependent (p = 0.003).6 CDR system Episodic Memory has been proven to be extremely correlated (70%) with the ADAS-Cog rating (r = 0.7).7 The calculated corresponding ADAS-Cog imply change from baseline rating is -1.9 (enchancment) for sufferers in the 50 mg dose group, an 8% imply enchancment from baseline to 14 weeks. The distinction between the ANAVEX®2-73 group and the placebo group in the change from baseline at 14 weeks was a 4.0-point enchancment of calculated corresponding ADAS-Cog rating (p = 0.015).
The Mini-Mental State Exam (MMSE) and the ADAS-Cog (Alzheimer’s Disease Assessment Scale–Cognitive Subscale) are normal assessments for assessing adjustments in cognition in Alzheimer’s illness trials and recognized to correlate to a excessive diploma.8 The ADCS-ADL (Alzheimer’s Disease Cooperative Study–Activities of Daily Living), assesses the competence of sufferers with Alzheimer’s illness in primary and instrumental perform or actions of day by day dwelling.
Alzheimer’s is a progressive illness and over time, a affected person’s cognition will all the time worsen. “Experience based mostly on longitudinal research of ambulatory sufferers with gentle to reasonable Alzheimer’s illness counsel that scores on the ADAS-cog worsen by 6-12 factors per yr” with the annualized charge of decline is likely to be smaller relying on the illness stage, in line with FDA’s Prescription Information sheet for ARICEPT® (donepezil), a drug accepted for the therapy of dementia of the Alzheimer’s sort.9
While the placebo-controlled 450-patient Phase 2b/3 ANAVEX®2-73 scientific research in Alzheimer’s illness is at present ongoing, prior scientific analysis in Alzheimer’s illness carried out by different sponsors can serve as a contextual reference for estimates of an anticipated charge of decline in cognition (MMSE and ADAS-Cog) and perform (ADCS-ADL) in placebo sufferers:
- In 2019, a randomized managed trial of aducanumab (Biogen) was carried out in >1,000 sufferers with early Alzheimer’s illness.10 In this Phase 3 research (EMERGE), sufferers on placebo confirmed from baseline to week 50 a imply decline in cognition of roughly -2.2 factors on MMSE, an 8.3% decline, and from baseline to week 78 roughly -3.3 factors on MMSE, a 12.5% decline, respectively. Mean baseline MMSE rating was 26.4.
- Large placebo arm information from 20 randomized managed scientific trials together with over 4500 mild-to-moderate Alzheimer’s illness sufferers handled with normal of care, containing ARICEPT® (donepezil, Eisai) and memantine was analyzed.11 In this evaluation, sufferers on placebo confirmed from baseline to week 52 a imply decline in cognition of roughly -2.05 factors on MMSE, a 10% decline and from baseline to week 78 roughly -3.4 factors on MMSE, a 16% decline, respectively, with a calculated imply baseline MMSE rating of 21.0. The respective ADAS-Cog decline was 3.9 factors from baseline to week 52 and a decline of 6.6 factors from baseline to week 78, respectively.
- A randomized managed research together with of ARICEPT® (donepezil, Eisai) and memantine was carried out in >500 sufferers in the placebo arm with mild-to-moderate Alzheimer’s illness.12 In this Phase 3 research, sufferers on placebo confirmed from baseline to week 76 an estimated imply decline in cognition of roughly -3.4 factors on MMSE, a 16% decline from baseline. Mean baseline MMSE rating was 20.9. The imply ADAS-Cog decline was 6.4 factors from baseline to week 76. The imply ADCS-ADL decline was -9.0 factors from baseline to week 76.
ANAVEX®2-73 is at present in a late-stage Phase 2b/3 Alzheimer’s illness scientific trial using identical dosing routine as in the above-described accomplished Parkinson’s illness dementia (ANAVEX2-73-PDD-001) research with differentiated affected person choice standards.13
“This paper highlights the relevance of the analyses of gene expression information in precision drugs to drug improvement that will predict elevated probabilities of success of Alzheimer’s illness remedies, which is particularly related in late-stage scientific research like the continuing ANAVEX®2-73 Phase 2b/3 scientific Alzheimer’s illness research,” stated Christopher U Missling, PhD, President and Chief Executive Officer of Anavex.
ANAVEX®2-73 prompts the sigma-1 receptor (SIGMAR1). Data means that activation of SIGMAR1 outcomes in the restoration of full housekeeping perform throughout the physique and is pivotal to restoring neural cell homeostasis and selling neuroplasticity.14
Anavex Life Sciences’ product portfolio consists of small molecule drug lead candidate ANAVEX®2-73 for the therapy of Alzheimer’s illness, Parkinson’s illness and Rett syndrome.
About Alzheimer’s Disease
Alzheimer’s illness is a progressive degenerative mind dysfunction that step by step destroys a individual’s reminiscence and capability to be taught, motive, make judgments, talk and perform day by day actions. An estimated 5.7 million Americans have at present Alzheimer’s dementia. Alzheimer’s is the most typical explanation for dementia amongst older adults and is estimated to rank as the third main explanation for dying for older individuals in the United States, simply behind coronary heart illness and most cancers. In 2020, Alzheimer’s and different dementias value the nation $305 billion. By 2050, these prices might rise as excessive as $1.1 trillion.15 There are at present over 50 million individuals dwelling with dementia around the globe, with numbers anticipated to extend to almost 152 million by 2050.16 Almost 10 million new circumstances of dementia are recognized every year worldwide, implying one new case each 3 seconds, and a important improve in the caregiving burden positioned on society and households.17
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical firm devoted to the event of differentiated therapeutics for the therapy of neurodegenerative and neurodevelopmental problems together with Alzheimer’s illness, Parkinson’s illness, Rett syndrome and different central nervous system (CNS) ailments, ache and numerous kinds of most cancers. Anavex’s lead drug candidate, ANAVEX®2-73 (blarcamesine), lately accomplished efficiently a Phase 2a scientific trials for Alzheimer’s illness and a Phase 2 proof-of-concept research in Parkinson’s illness dementia and a Phase 2 research in grownup sufferers with Rett syndrome. ANAVEX®2-73 is an orally obtainable drug candidate that restores mobile homeostasis by concentrating on sigma-1 and muscarinic receptors. Preclinical research demonstrated its potential to halt and/or reverse the course of Alzheimer’s illness. ANAVEX®2-73 additionally exhibited anticonvulsant, anti-amnesic, neuroprotective and anti-depressant properties in animal fashions, indicating its potential to deal with extra CNS problems, together with epilepsy. The Michael J. Fox Foundation for Parkinson’s Research beforehand awarded Anavex a analysis grant, which absolutely funded a preclinical research to develop ANAVEX®2-73 for the therapy of Parkinson’s illness. ANAVEX®3-71, which targets sigma-1 and muscarinic receptors, is a promising scientific stage drug candidate demonstrating disease-modifying exercise towards the most important hallmarks of Alzheimer’s illness in transgenic (3xTg-AD) mice, together with cognitive deficits, amyloid and tau pathologies. In preclinical trials, ANAVEX®3-71 has proven helpful results on mitochondrial dysfunction and neuroinflammation. Further info is obtainable at www.anavex.com. You may also join with the corporate on Twitter, Facebook and LinkedIn.
Statements in this press launch that aren’t strictly historic in nature are forward-looking statements. These statements are solely predictions based mostly on present info and expectations and contain a variety of dangers and uncertainties. Actual occasions or outcomes might differ materially from these projected in any of such statements because of numerous elements, together with the dangers set forth in the Company’s most up-to-date Annual Report on Form 10-Ok filed with the SEC. Readers are cautioned to not place undue reliance on these forward-looking statements, which communicate solely as of the date hereof. All forward-looking statements are certified in their entirety by this cautionary assertion and Anavex Life Sciences Corp. undertakes no obligation to revise or replace this press launch to mirror occasions or circumstances after the date hereof.
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1 Hampel H, Vergallo A, Caraci F, Cuello AC, Lemercier P, Vellas B, Giudici KV, Baldacci F, Hänisch B, Haberkamp M, Broich Ok, Nisticò R, Emanuele E, Llavero F, Zugaza JL, Lucía A, Giacobini E, Lista S; Alzheimer Precision Medicine Initiative. Future avenues for Alzheimer’s illness detection and remedy: liquid biopsy, intracellular signaling modulation, techniques pharmacology drug discovery. Neuropharmacology. 2021 Mar 1;185:108081. doi: 10.1016/j.neuropharm.2020.108081. Epub 2020 May 11. PMID: 32407924.
3 ClinicalTrials.gov Identifier: NCT03790709.
4 Hampel H. et al., 2018. Full genomic evaluation of ANAVEX®2-73 part 2a Alzheimer’s illness research identifies biomarkers enabling focused remedy and a precision drugs method. Alzheimer’s & Dementia 14, P1519–P1520. https://doi.org/10.1016/j.jalz.2018.07.027.
5 Hampel H. et al. (2020). A precision drugs framework utilizing synthetic intelligence for the identification and affirmation of genomic biomarkers of response to an Alzheimer’s illness remedy: Analysis of the blarcamesine (ANAVEX2‐73) Phase 2a scientific research. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 6(1), e12013.
7 Wesnes Ok. et al., Computerized cognition evaluation throughout acetylcholinesterase inhibitor therapy in Alzheimer’s illness. Acta Neurol Scand 2010; 122:270–7.
8 Solomon T.M. et al., Correlational evaluation of 5 generally used measures of cognitive functioning and psychological standing: an replace. 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 research, 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 illness: Analyses of placebo information from scientific trials. Alz & Dem 2016; 12: 598-603
12 Doody RS et al. (2013) N Engl J Med; 369:341-350
13 ClinicalTrials.gov Identifier: NCT03790709
14 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/well being/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.