Anavex Life Sciences Corp (AVXL)

[Doc328]

The original endpoint from December 2018 until September 2021 was:

1.	ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) 
 [ Time Frame: 48 weeks ] 
  
 Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo 
 2.	ADCS-ADL (Activities of Daily Living) 
 [ Time Frame: 48 weeks ] 
  
 Changes from baseline to week 48 in ability to perform daily activities according to the Activities of Daily Living Scale (ADCS-ADL) compared to placebo 
 

The last update, July 12, 2022 was:

1.	ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [ Time Frame: 48 weeks ] 
 Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) 
  
 2.	ADCS-ADL (Activities of Daily Living) [ Time Frame: 48 weeks ] 
 Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL) 
 

Looking at a few other studies, the most common wording for AD trials endpoints is "Change from baseline". This was also the wording used for aducanumab's trials -- that led to FD approval, So the original wording was "Change from baseline", the gold approvable standard and now its "Reduction in cognitive decline assessed from baseline over 48 weeks" Of course we care about good outcomes so, on the surface, reduction from baseline sounds like its just excluding "worsening from baseline" That seems ok though it may lead to an attempt to use one-sided rather than 2-sided p values which is not the standard. The other strange part is the change in prepositional phrase from "from baseline to 48 weeks" to "from baseline over 48 weeks". Is "to" to "over" just a choice of wording or are they planning some sort of AUC type analysis which might be fine as long as the original endpoint is also released. Failing to do so will lead to another Avatar fiasco. Just my concern, I may be reading too much into the semantics.