First Impressions from CTAD 2019 Presentation. $AVXL Blarcamesine

Don’t trade this post
as 4 billion years of evolution and
possibly God is against my judgment

 

 

The beginning of the presentation dwells on advancement in clinical studies beyond the slow process of adding sources of information to process which might have not changed for decades towards a revolution.  It seems that now due to the availability of data placebo arm might be eliminated and the evaluation of efficacy and safety might be dynamic (adaptive) that is done in real-time i.e. responding to changes in the data.

I will leave this to more knowledgeable people and let’s graph some adjusted lines on paper for fun.

Before I do this, let me show you what I got in response to my blog (the previous post on Blarcamesine):

Tweet aboy blog AVXL

I am not petulant, and I have to give partial credit to this gentleman.  Since my training is in engineering I can say that I am not a scientist.  I have been told that an engineer needs to get to +/- 20% of the real-world numbers in his model of reality.   If you want to do something in this field of the human endeavor, you model something, or use some heuristics (rules of thumb), and then validate model just test what you build and if everything works out you call it a success if not you go back to your model and start thinking harder.

I know that I am not exactly right but I am not entirely wrong either.  A number of people who were called geniuses were lionized in the public minds. When you read their biographies the success is the result of much efforts and some of these attempts might not be rewarded as the public tends to think.   If somebody tells you that you are smart, run away because humans have their limitations and could be easily duped.  However, limited my thinking is it is really fun to get on a limb and theorize, extrapolate, play with numbers and make yourself look plain stupid.  At least you don’t watch TV.

At now back to the main program:

CTAD 2019 Presentation page 13 APOEe4 gene occurance

  • The carries of APOE e4 deteriorate quicker but they also get Alzheimer’s when they are younger.
  • In a simple search, I did not find any clear number to assess the amount of acceleration in decline vs. noncarriers.
  • The difference in the prevalence of APOE e4 gene in ADNI Placebo vs. High Concentration A2-73 is -27%.
  • The ADNI Placebo Arm fidelity to Phase 2a conditions is limited by the data gathered by the organization. Only 104 weeks of data available and mismatch on APOE e4 carriers prevalence.

Let us go to the next slide:

CTAD 2019 104 week a2-73 data to adjustent for APOE e4

  • There are trend lines for Low & Medium and ADNI Placebo. Since there is 0.47 point difference between these at 104 weeks we can make assumptions about the bias due to the impact of the prevalence of APOE e4.  (30% and 48% respectively)
  • Simple grammar school math gives us (y=+.3525*x+20) bias to be applied to High Concentration trend line (y= -.5500*x+20)

Let’s see the adjusted Blaracamesine trend line.  (this is just a trend line, nothing more):

CTAD 2019 adjusted for APOe e4 gene

More info can be found in the previous post about Blarcamesine and $AVXL regarding the colors of different trend lines and how they were generated.

  • The top continuous black line depicts adjusted for APOE e4 bias the High Concentration trend line.
  • The trend line runs so close to the line for MMSE=20 that the portion of that line was removed.
  • After 6 years the drop would be -1.2 MMSE points.
  • The previous unadjusted line would be -3.2 MMSE points.
  • The unadjusted but extrapolation attempting to account for accelerated deterioration would be at -6.7 MMSE points.
  • APOE e4 is present in 15% of the population and increases the probability to have Alzheimer’s disease 12 times.
  • By attempting to apply the bias to the High Concentration trendline the comparison with ADNI Placebo is more realistic. After 6 years there is a projected 1000% greater deterioration in Placebo Arm than Blarcamesine patients of identical groups of patients.

In the process of making this exercise, no patient was harmed and if I were wrong only I would look stupid.  This is in the realm of possibilities but not a certainty.

One word here, I realize that extrapolations in the physical world are rather dumb.  Most biological systems are comprised of elements and under the influence of so many factors that highly non-linear behavior is possible, and each of us has experienced this with our health 9this wisdom comes with age).  The word non-linear means in vernacular that you wake up one day and you feel sick or health all of sudden.  Yet, $AVXL did extrapolate the ADNI trend line to 148 weeks.  LOL. I bet that they are just mocking me since I have been doing it for a time.

I hope that this gives you insight into the possible factors involved in the evaluation of trial results.  I know that the real curves for the deterioration of Alzheimer’s patients are much more complex as they involve dropout as well as MMSE scores decline.  Now I am waiting for my 15 minutes of fame! LOL. With a beer in my hand.

Beer Fund

$1.00 is about one bottle so .....please contribute..

$1.00

 

 

 

 

 

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