What To Expect from $CRTX and Atuzaginstat at CTAD 2021 $AVXL $SAVA

Do not trade this blog as 4 billion years of evolution is against me and possibly even God laughs at it, He has a great sense of humor!

An Illustration….

X-axis is in weeks of dosing, y-axis is in MMSE points and the number 30 represents the highest score.

HowI Got There….

  • I took the best four patients who never declined from the group of the Superperformers from phase 2a and calculated their baseline average and then their changes in time (weeks) on MMSE scale. (Blarcamesine)($AVXL). From the way this group is defined by biomarkers it should be composed of ~44% of AD population. This should model the best possible outcome for Blarcamesine patient. [1]
  • I did similar thing with Simufilam data ($SAVA) but I only limited it to those 64% patients who never declined and divided the ADAS-Cog11 numbers by crude proportionality ratio of 2.33 between the 70 point ADAS-Cog11 and 30 MMSE scales. I anchored the Simufilam data at 22.5 MMSE which is the same as Blarcamesine average baseline. This should model the best outcome for a Simufilam patient. 32 patients out of 50 at the mark of 9 months.

From the previous trials of Blarcamesine, Simufilam, Donezepil and many others, one can see that the responce to various drugs usually is very rapid and then we either have rollover and reassumption of decline and deterioration in cognition scores or like in the case of Blarcamesine rapid improvement followed by slower rate of the same. Simufilam is the most puzzling as it starts slowly then accelerates to only prepare to rollover into deterioration or if things turn for the better to stagnate. Let’s see an illustration in ADAS-Cog11 sores so negative scores are indicating improvement.

Of course, this is the average for all the 50 patients.

$CRTX shall soon provide us witht the data on its GAIN trial. The composition of the baseline population is much diffrent from those present in Blarcamesine Phase 2b/3 and Simufilam Open Label. It is 50% between 12 and 18 MMSE and 50% between 19 and 24. It is difficult to rescue those lower scoring on MMSE scale. So the success of the trial can be best defined by the extend by which the number of the patients are helped/rescued out the total number of the patients. In case of Blarcamesine the number now has been theoretically assumed to be 44%. For Sumufilam the number was at 6 month 90-something% but now has decreased 64%. At the 12 months either the improvement scores don’t go up any more or some patients start crossing from those help/rescued to those who have actually declined. As $CRTX claimes that 90% AD sufferers are also carriers of P. gingivalis in their brains, and this being behind the onset of the disease then Atuzaginstat should affect almost all these patients, but that should not to be expacted to be to the same degree. The other aspect of the antoicipated rescue of AD in the GAIN trial is that 50% should see at the least improvements similar to Blarcamesine 44%. That is their MMSE scores should go up about 3.5 points from baseline. The other 50% scores should be lower, by let’s say 50%, but the further decline should be about 10% of the overall population.

The above number should give ~2.2 MMSE average score and Effect Size Cohen’s d about 2.0 (huge).

I hope the results will be even better. The most important part is the precentage of the patients who were stopped from decline as this validates the P ginvivalis etiology of AD. Let’s wait for November 11th to find out. Good luck to all.

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[1] https://piotrpeterblog.com/2021/09/30/can-blarcamesine-catch-up-to-simufilam-and-surpass-it-avxl-sava-ctrx/

[2] https://piotrpeterblog.com/2021/09/27/why-sava-simufilam-might-not-have-any-advantage-over-avxl-blarcamesine-sava-avxl-crtx-snpx/

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