Anavex Life Scienceshas announced late breaking oral communication at CTAD 2019, by presenting the 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, 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).