Why Placebo Arm Is Critical To Proper Assesment Of Therapeutic Effect In Trials Of Alzheimer’s Disease. The Case of Phase2b/3 For Blarcamesine (Anavex2-73) And Simufilam Open Label. $AVXL $SAVA

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The following post is in reference to paper tilted:

link: https://alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2010.03.018

The purpose of this paper is to establish realtionship between covariates like baseline severity, age, APOE4 genotype and gender, and the slope of yearly decline in ADAS-Cog cognition measure.

The Conclusions Most Relevant To Investors:

• The mean slope is dependent mostly on baseline severity and age.
• The individual slope is dependent on APOE4 genotype (incease of ~22% deterioration) and the gender; male decrease of ~10% in deterioration vs. females.

To illustrate the impact the baseline severity and age can have on the first year decline slope can have one can peruse or parse the table 3 from the above paper.

If we are to compare results from Blarcamesine ($AVXL) Phase 2b/3 and Open Label Simufilam ($SAVA) following information can be gathered from the data published by the comapnies.

For Simufilam: Baseline Mean ADAS-Cog 16.7(+/-7.86); Age 69.6 (+/-6.4)

For Blarcamesine (dosed Cohorts): Baseline Mean ADAS-Cog ~29.0 (+/-8.80); Age ~73.9 (+/-6.5)

Neither of these sets of values neatly fall into the ones listed in the table.

Blarcamesine is closer to record listed as 30 ADAS-Cog baseline and 75 years of age, where as Simufilam Open Label is closer 20 ADAS-Cog baseline and Age of 70 years. The disparity of the decline slopes is ~3.6 ADAS-Cog points with potentially Blarcamesine population declining faster than Simufilam. One can infere from the table that the baseline severity carries more weight than just the age. The difference between Blarcamesine and Simufilam is greatest in the baseline severity than in the age. However, the only firm conclusions we can draw from the table is that studies are more difficult to compare if their demographics vary significantly and that they should be evaluated in context of their own placebo arms to avoid the bias introduced by the diffrences in demographics.