$BIIB $AVXL I confess: I dismissed BIIB037 as irrelevant, yet I still can be right….

I dismissed any talk about possibility of success of monoclonal antibodies in targeting Amyloid Plaque in Alzheimer.  Mea Culpa Maxima! Sometimes one has to make about-face, and acknowledge that BIIB037 does prove something.  In Alzheimer model, from this reference Ref 1 3D model of Alzheimer in vitro , the Amyloid Plaque appears after incubation and causes the inflammation (due to action of innate immune system) to proceed with destruction of the neurons and atrocities which nurture them.  From the results of trial one might think that Amyloid Plaque once cleared can make the disease either stop or slow down.  At least that is what number of companies claim and try to prove with their work.  If indeed BIIB037 can stop decline then it seems that the homeostasis disturbance does not by itself calls for inflammation, and this stage the culprit here might be Amyloid Plaque which alone draws immune system in.

  1. The data on MMSE score for patients selected with the four criteria in CTAD 2018  presentation (page 12 & 13) for ANAVEX 2-73 Δ=-1.8 over 2 years 10 months (148 weeks) (no info on dropouts ) (Blue)
  2. The same for BIIB037 over 3 years and 4 years. (no info on dropouts ) (Black)
  3. The MMSE scores for remaining in the study patients over 4 years (average) (Red). Ref 2: Alzheimer’s Natural Course

Biogen AVXL Placebo.png

This is for the case of relative start from the same level about 21 MMSE (Mild to Moderate)

This is relative performance but it can not be compared as each of those caries different profile of so-called dropouts.  These are patients who decline so rapidly that they stop reporting to investigators or are placed in institutions.  The dropout dynamic can be seen for line #3 in this post Illustration of dropout rate in Alzheimer studies.

There is one thing that is salient in article about BIIB037 and that is the “Adjusted Mean”. Well adjusted mean might correct small distortion due to uncontrollable variable and might not alter the meaning of the data or can “overwhelm” the initial data with its correction.  There is not further explanation to that so I still might be right not to show some contrition on my parts.

 

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