Baseline-matched Real-World external Control Data with Alzheimer’s Disease Neuroimaging Initiative (ADNI): ANAVEX®2-73 (blarcamesine) Cohort showed a Significantly lower Cognitive Decline Compared to the ADNI Control Cohort at Interim 2-Year (104-Week) Timepoint
Abundance of Lachnospiraceae and Enterobacteriaceae Families as Potential Biomarker of Response from a 2-Year Study Interim Clinical Data Analysis of ANAVEX®2- 73 (blarcamesine)
NEW YORK – December 4, 2019
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 announced Late Breaking Oral Communication at CTAD 2019.
Interim 2-Year (104)-Week) data from the Phase 2a ANAVEX®2-73 (blarcamesine) extension study, with Alzheimer’s disease patients followed for up to five years, will be presented at the 12th Clinical Trials On Alzheimer’s Disease (CTAD) 2019 Conference in San Diego, CA (December 4-7, 2019).
“These results confirm the rationale to advance the ANAVEX®2-73 (blarcamesine) Alzheimer’s disease program through the ongoing Phase 2b/3 Alzheimer’s disease clinical study[1],” said Christopher U. Missling, Ph.D., Chief Executive Officer of Anavex. “The data also establishes the findings of two further gut microbiota family biomarkers linked to improved response with ANAVEX®2-73 (blarcamesine).”
FDA’s Framework for Real World Evidence document released in December 2018 demonstrates how Real World Evidence can be incorporated into regulatory decision-making. This framework was applied to the study of ANAVEX®2-73 (blarcamesine), a selective sigma-1 receptor (SIGMAR1) agonist that was investigated in an open-label 57-week Phase 2a study of Alzheimer’s Disease (AD) patients (N=32) showing a favourable safety profile (NCT02244541) and was further extended by 208 weeks (NCT02756858). A hypothesis free data-driven analysis using Formal Concept Analysis Machine Learning as implemented in Knowledge Extraction and Management (KEM) software platform was used to identify exploratory efficacy and patient selection biomarkers including SIGMAR1 p.Q2P (rs1800866).
The goal of this study was to evaluate the efficacy of ANAVEX®2-73 (blarcamesine), measured by Mini Mental State Examination (MMSE) and comparing treated patients with an external control AD cohort of patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database over a 104-week period.
Individual patient-level data (IPD) was obtained from the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is a longitudinal multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of AD. A total of 1891 patients were followed in this study including 345 AD patients with available MMSE scores.
Propensity score matching (PSM) was applied using Linear Mixed Effects (LME) models including descriptors of age, sex, SIGMAR1 p.Q2P carrier status, APOE4 allele and MMSE at baseline to select patients with similar baseline characteristics and any confounding factors between AD patients in the Phase 2a ANAVEX®2-73 (blarcamesine) cohort and AD patients from the ADNI control cohort.
Change in MMSE score from baseline at week 104 of matched cohorts was assessed. It showed that ANAVEX®2-73 (blarcamesine) high dose cohort had a significantly lower MMSE decline (-1.1) compared to the ADNI control cohort (-4.4) at week 104 (p < 0.01).
The presentations at CTAD 2019 include:
Oral presentation [LB20]: Novel analytics framework for augmenting single-arm Phase 2a open label trials with Real-World external control data: Application to the Blarcamesine (ANAVEX®2-73) study in Alzheimer’s disease matched with propensity corrected patients from Alzheimer’s Disease Neuroimaging Initiative (ADNI) exploring treatment effect on cognition at interim two-year (104-Week) timepoint[2]
Poster presentation [P84]: Gut Microbiota and Response to Blarcamesine (ANAVEX®2-73) in Alzheimer’s Disease Patients: Abundance of Lachnospiraceae and Enterobacteriaceae Families as Potential Biomarker of Response from a 2-Year Study Interim Clinical Data Analysis using KEM Artificial Intelligence[3]
The presentations will be accessible through the investor relations section of the Company’s website at www.anavex.com.
About ANAVEX®2-73 (blarcamesine)
ANAVEX®2-73 activates the Sigma-1 receptor (S1R) protein, which serves as a molecular chaperone and functional modulator involved in restoring homeostasis. S1R activation has demonstrated ability to reduce key pathophysiological signs of Alzheimer’s disease: beta amyloid, hyperphosphorylated tau, and increased inflammation. In a Phase 2a Alzheimer’s disease (AD) study, ANAVEX®2-73 (blarcamesine) has shown dose dependent improvement in exploratory endpoints of cognition (MMSE) and function (ADCS-ADL). Full genomic analysis of ANAVEX®2-73 Phase 2a AD patients was performed. A 48-week Phase 2b/3 study of ANAVEX®2-73 (blarcamesine) in 450 patients with early Alzheimer’s disease is ongoing.
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 a successful Phase 2a clinical trial for Alzheimer’s disease. ANAVEX®2-73 (blarcamesine) 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 (blarcamesine) 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 (blarcamesine) for the treatment of Parkinson’s disease. ANAVEX®3-71, which targets sigma-1 and muscarinic receptors, is a promising preclinical 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.
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