P1‐046: New Exploratory Alzheimer’S Drug Anavex 2‐73: Dose Dependent Clinical Cognitive Improvement Observed in Mini Mental State Examination (MMSE) and Other Cognitive Markers in a Phase 2A Study in Mild‐to‐Moderate Alzheimer’s Patients

Abstract

ANAVEX2-73, a sigma-1 and muscarinic receptor agonist was tested in a Phase 2a study. Safety, MMSE and other cognitive markers (Cogstate, QEEG/ERP) as well as functional markers like ADCS-ADL were measured in subjects with mild-to-moderated AD. Thirty-two AD subjects 55-85 years old with MMSE between 16 and 28 were recruited. In PART A of the study, participants were randomized and administered ANAVEX2-73 in an open-label, 2-period, cross-over, adaptive study design lasting up to 5 weeks. In PART B all subjects are administered ANAVEX2-73 daily orally and re-assessed at 12, 26, 38, and 52 weeks. By the time of the AAIC conference data for 12 and 26 week will be available. PART A: Analysis of Variance on the five week data reveals that the treatment effect remains the only factor that significantly influences the MMSE- (p=0.0285) and ERPΔ-scores (p=0.0168). Those results were confirmed with post-hoctests and Bayesian hierarchical analysis. Robust linear regression was performed for efficacy MMSE and ERPΔ-scores vs. ANAVEX2-73 doses. A significant positive slope for the ANAVEX2-73 dose was identified. The 95% confidence interval clearly excludes the zero-value. Bootstrap confirmed the positive slope and the confidence intervals that also exclude the zero-value. The regression involved also all available predictors, i.e., age, donepezil (DPZ) co-administration and sex; their impact on the Δ-scores efficacy was analyzed. For MMSE, the only significant predictor was the ANAVEX2-73 dose (p=0.003), whereas for ERP, both ANAVEX2-73 and the DPZ doses were revealed significant as predictors (p=0.014 and p=0.026, respectively). PART B: The longitudinal effect of ANAVEX2-73 for up to 26 week, including MMSE and ADCS-ADL measures, which find also utilization as primary endpoints in registration studies, will be provided at the time of the conference. Results from the clinical trial show that ANAVEX2-73 dose-dependently affects cognitive performance in patients with mild-to-moderate AD. The safety of ANAVEX2-73 is also being assessed and thus far shows that the drug is well tolerated with only mild and moderate adverse events to report. The data collected so far supports further clinical development of ANAVEX2-73. A more complete set of results will be available at the time of the conference.