Anavex Life Sciences Corp (AVXL)

[TempePhil]

Comparison of published A2-73 AZ 57wk data to current AZ trial
5/16/2019
A week ago, Nidan posted a link to a good Nuerology article at mdedge (Feb.2017), which is based on 57 weeks of data for the original A2-73 safety patients. It is based on the Prof.Stephen Macfarlane Anavex presentation. Though this article is a little dated, this is still some of the best data we have at this time for estimating AZ trial success.
https://www.mdedge.com/neurology/article/130412/alzheimers-cognition/can-sigma-1-agonist-stabilize-cognition-and-function
Nuerology article at mdedge

Below is a comparison of the current Alzheimers Phase 2b/3 trial outcomes/endpoints, and the Safety trial 57wk data for the original A2-73 safety patients. The purpose of this post is to connect some of these dots.

Current Phase 2b/3 48wk trial-Primary Outcomes:
1. ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition)
-----57 week Safety trial result-- At week 31, statistically significant improvements of processing speed, attention, and memory, were seen(per article). (Likely the reason for the trial being 48wks!) Also, a similar test called Mini-Mental State Examination(MMSE) was used. “The MMSE declined 45%...less than what we would have expected from the historical control data,” Dr. Macfarlane.

2. ADCS-ADL (Activities of Daily Living)
-----57 week Safety trial result-- "...the ADCS-ADL declined 56% less than what we would have expected from the historical control data,” Dr. Macfarlane.


Current Phase 2b/3 48wk trial-Secondary Outcomes
1. Adverse events
-----57 week Safety trial result-- "Nearly all patients (98%) experienced an adverse event. Most events were mild, transitory dizziness or headache...", per the mdedge article.

2. Clinical Dementia Rating Scale Sum of Boxes
-----57 week Safety trial result-- no data.

3. RSCAQ sleep score
-----57 week Safety trial result-- "Any patient who scored on the insomnia measure [of the Hamilton Depression Rating Scale] at baseline had no sleep disturbance at all by weeks 12 and 26,” Stephen Macfarlane.

The upcoming peer review article will likely have similar data (as this was the data collected to 57 weeks), but be for two years and hopefully show further improvements.

Curiously, what appears to be very encouraging Electrophysiologic measurement data (P300), from the 57wk study, was not included in the current trial as an endpoint or even as a measurement. Doc328 and I analyzed the A2-73 for treatment of AZ patent app 20180360796, regarding the electrophysiologic data, and concluded that it did not make sense. Most likely, because the patent info only went to 5 weeks, and was statistically insignificant. This seems like good quantitative data that one would want in go/nogo type trials. Maybe Anavex did not have the confidence, or was not prepared, to include them in the AZ trial. Prof.Macfarlane will probably collect this data on all his patients in AZ (just my guess!).