A Bit About MDS-UPDRS $AVXL $ANVS

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!

Data on Parkinson’s MDS-UPDRS Measure from $ANVS.

There are 4 parts to this test. Part 1 deals general mood. From the slide it is obvious that there is improvemnt in the placebo like the dosed cohort; conclusion strong placebo effect. The difference is large as it is about 9%. Part 2 is asking patients for their daily living activities, and again placebo effect is large with minimal difference odf 1%. Part 3 monitors the deterioration in the eponimous with Parkinson’s patients motion capabilities. the improvent here is absolute 2% and relative to placebo 3%. Forth part deals with complications in the therapy, patients are usually on some therapy, and there is lower incidence of perceived therapy problems in dosed cohort by 3%.

The consequitive parts have a ratio of the mean partial scores making up for the total over all mean score: 12.2:14.5:34.4:3.5 [1]. The part 1 and part 4 a can be connected by the improvement in cognition, ratio is 3.5. The part 2 and 3 are similarly correlated with ratio 2.37 as they are different take on the basic motion and dementia ability.

The ratio of all improvements is 9:1.1:3:2.8. This implies former ratio to be 3.2 and the latter to be 2.7. If we recalculate this we get (12.2*.09)+(14.5*1.1)+(34.4*.03)+(3.5*.028)=~2.4 points improvement.

Let’s make another assumption. The trial took 25 days, what if the trial is extended to 14 weeks and the progress in improvement is linear (my foot, but for a lack of better model this will do in this exercise).

(14*7)/25=3.92 3.92*2.4=~9.4 points improvement in 14 weeks (linear)

I bet, God is laughing now!

Let’s compare this to $AVXL’s Blarcamesine. See the results at this link: https://www.anavex.com/anavex-life-sciences-announces-anavex2-73-blarcamesine-improved-both-primary-cognitive-and-secondary-mds-updrs-efficacy-endpoints-with-significant-biomarker-correlation-in-placebo-controlled-p/

Blarcamesine did in 14 weeks 14.51 points of improvement.

This is all great but the unpredictable thing is the waning off the placebo effect which seems to be in full swing at 25 day of the $ANVS trial.

One thing is how the numbers make a partial sense, and the other thing is that there is a danger that the improvement in motion abilities of patients is smaller than one would expect because of the disproportionally better scores in parts 1 and 4. This can be blamed on the better mood and cognition these drugs induce in the patients. No doubt that the parts 1 and 4 are partialy tied to each other, as might also be the case with parts 2 and 3. $AVXL has not released such data. It would be very interesting to see it presented in some way similar to $ANVS. On the other hand, it just suffices to keep the motion abilities of the patients from further deterioration so that with time the patient will stabilize as they are mostly mild or moderate at this stage of the disease.

Data on composition of mean Parkinson’s score comes from paper Differences in MDS-UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration [1] link: https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mdc3.12476

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