Benzinga | Jul 29, 2021 07:02AM EDT

Anavex Life Sciences Reports Data Showing 'Pre-Treatment with ANAVEX2-73 entirely prevented Abeta-induced cognitive decline'; Says Planning Phase 3 Prevention Trial

Pre-Treatment with ANAVEX(r)2-73 entirely prevented Abeta-induced cognitive decline



Anavex planning a Phase 3 prevention trial of ANAVEX(r)2-73 including participants at risk for cognitive and functional decline related to Alzheimer's disease

NEW YORK, July 29, 2021 (GLOBE NEWSWIRE) -- 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) disorders, today reported new data that established ANAVEX(r)2-73 to be a preventive treatment in the pharmacological model of Alzheimer's disease (AD). Pre-treatment with ANAVEX(r)2-73, repeated once daily for one week before the A? (Abeta) challenge was protective in the A?25-35 peptide model of Alzheimer's disease in mice. ANAVEX(r)2-73 significantly and dose-dependently prevented A?25-35-induced biomarker-correlated cognitive impairments, which were assessed one week after the A? (Abeta) insult during which no further ANAVEX(r)2-73 treatment took place.

ANAVEX(r)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.1 SIGMAR1 also promotes autophagy and results in the degradation of amyloid-beta precursor protein (APP) thereby inhibiting A? production2.

"We are excited about this data, which indicates the potential expansion for the ANAVEX(r)2-73 platform to find an effective Alzheimer's prevention therapy, which might benefit the entire field," said Christopher U. Missling, PhD, President & Chief Executive Officer of Anavex. "In addition to finding treatment options for Alzheimer's disease, we are also striving to find effective prevention therapies for this devastating disease, and this data might help advance this endeavor to address an area of high unmet medical need."

Data from this study will be submitted later this year for presentation at a scientific medical meeting.

Previously, a publication in Neuropharmacology noted that in a clinical study (ANAVEX2-73-002) of Alzheimer's disease patients, 57 weeks of oral once daily ANAVEX(r)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(r)2-73 also improved ADCS-ADL, by +4.9 points, a 7% mean improvement from baseline to 57 weeks.3

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(r)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(r)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(r)2-73, 50 mg ANAVEX(r)2-73 and placebo for 14 weeks. The observed statistically significant improvement of CDR system Episodic Memory of +42.22 between 50 mg ANAVEX(r)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(r)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 Company recently announced that it has exceeded its enrollment target for the ANAVEX(r)2-73 (blarcamesine) double-blind, placebo-controlled late-stage Phase 2b/3 study (ANAVEX2-73-004) in Alzheimer's disease.

Anavex Life Sciences' product portfolio platform includes orally available small molecule drug lead candidate ANAVEX(r)2-73 for the treatment of Alzheimer's disease, Parkinson's disease and Rett syndrome and ANAVEX(r)3-71 for frontotemporal dementia.