Anavex Life Sciences Corp (AVXL)

[sokol]

At least in the Blarcamesine Parkinson’s study Anavex previously reported (Aug. 2022) that “SIGMAR1 mRNA expression significantly increased in ANAVEX®2-73-treated patients vs placebo (p=0.035) over the course of treatment and was significantly associated with improvements of MDS-UPDRS scores and cognitive efficacy endpoints CDR system.”

Anavex said then that: “These findings will facilitate contextualization of upcoming readout of ANAVEX®2-73 Phase 2b/3 Alzheimer’s disease clinical trial”

ANAVEX®2-73 transcriptomics analysis (RNAseq) identified a gene network that is differentially expressed in Parkinson’s disease dementia (PDD) patients treated with ANAVEX®2-73 compared to placebo after 14 weeks of treatment. The expression of 14,150 genes were analyzed from both placebo and ANAVEX®2-73 treated patients. Biological relevance of this gene network was assessed through pathway analysis and confirmed the impact of ANAVEX®2-73 treatment on pathways involved in neurodegenerative diseases, especially Alzheimer’s disease and Parkinson’s disease.

While genes are known to be down-regulated in Alzheimer’s disease1 and Parkinson’s disease2, representing pathology for these diseases, ANAVEX®2-73 singularly impacted expression levels of these genes in multiple pathways by countering the pathological down-regulation of genes in both Alzheimer’s (p<0.005) and Parkinson’s disease (p<0.005) and other degenerative diseases (p<0.005).

The scope of these detected gene expressions identified through ANAVEX®2-73 effect may represent additional potential biomarkers of disease pathology and response.
Previously, this study demonstrated dose-dependent, statistically significant improvement of dementia assessment, Quality of Episodic Memory with ANAVEX®2-73 (p=0.003) as well as significant improvement of Parkinson’s assessment, MDS-UPDRS Total score (p=0.034), in patients treated with ANAVEX®2-73 high oral dose once daily during the 14-week trial. SIGMAR1 mRNA expression significantly increased in ANAVEX®2-73-treated patients vs placebo (p=0.035) over the course of treatment and was significantly associated with improvements of MDS-UPDRS scores and cognitive efficacy endpoints CDR system.3

https://www.rna-seqblog.com/rna-seq-identifies-treatment-impact-of-neurodegenerative-drug-anavex2-73/

So, Anavex is trying to correlate SIGMAR1 mRNA expression increase in ANAVEX®2-73-treated patients (maybe 30-50 patients?) as the biomarker to support approval of its drug for Alzheimer’s? If so, do you have any idea what the CDR-SB score may be for the 30-50 patients? Did anyone at CTAD have any opinion about that?