The thorn in the side of $AVXL investors explained. BIIB037 vs. Anavex 2-73

Again..

It is very hard to just by reading the improvement numbers from placebo to assess the drug’s performance (15% over MMSE or ADCS-ADL 40% scores).  The fundamental question is the base in the placebo performance.  I looked up some sources on the internet and as far as I remember and my old posts confirmed this placebo average MMSE scores for AD are declining -3.79/y, ADCS-ADL scores about -6.5/y.  In the graph below the performance of Anavex 2-73 was taken for the whole High Concentration Cohort so it is in this case not adjusted for the genetic markers so includes the fast decliners.  The slope of Anavex 2-73 was derived from 109 weeks results. The plot is extrapolated to 6 years.  The progress of the disease in this graph is very general and might differ from the real trials.

MMSE SCORE for BIIB037 and A2-73 as of 10-23-2019

Most trials are starting from about MMSE 20 score, which corresponds to ADCS-ADL 55.

Another graph depicted the general extrapolated decline of ADCS-ADL scores for the same drugs, with the difference that the Anavex 2-73 decline is from 148 weeks data and corrected (I need to check it, I don’t remember now) for genetic markers. Again, the starting point is the corresponding score (theoretically) to standard trial.

 

ADCS-ADL SCORE for BIIB037 and A2-73 as of 10-23-2019 copy

 

Discussion

  1. The decline for Anavex 2-73 in ADCS-ADL sores is so small that when we take into consideration the advanced age of most subjects in those trials (70-80) it means that they are more likely to die or become dependent due to other causes than AD.  The MMSE scores which certainly do not include correction for the genetic markers to a great degree corroborate this assertion.
  2. BIIB037 improves the prospects of the patients to a degree, yet I would exercise caution here.  The study has only looked into 18 months of dosing vs. Anavex 2-73 for almost 3 years, the data collected to produce the slope of ADCS-ADL scores.  Extrapolation has its limits.
  3. BIIB037 can stand on his own if this extrapolation of further benefits holds but it can not beat the results of Anavex 2-73.  The safety of the monoclonal antibodies targeting the plaque up to now was a mixed bag and some had serious side effects.  At this point, after 5 years of dosing, Anavex2-73 has not been implicated in some sort of serious side effect.  The difference between these drugs, approaches, can not be overstated.

 

I hope that this is not the last post and that it will survive the horror of Halloween.  Can you spare a beer?

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