Who is Following Whose Success? $SAVA $ANVS $AVXL

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$SAVA Success Wave Lifting All Boats

The released $SAVA data brought about a wave of investment and renewed vigour to investing into smaller Alzheimer’s narratives. When most of the news is just shadowing the declines and any number above the initail score is reason for hope. A couple of things are transpiring among the companies searching for Alzheimer’s drugs. One, and the most impoortant is that most of them focused on MCI (Mild Cognitive Impairment) patients with MMSE scores 25 or ADAS-Cog11 15. This is a big departure from looking into average score of 21 MMSE points as it was done by $AVXL 5 years ago. It was learned the hard way that Mild to Moderate Alzheimer’s patient (16-25 MMSE) do not respond readily to experimental drugs as it was expected. For $AVXL drug Blarcamesine the cut-off MMSE score is 20. In the words of Dr Missling $AVXL “can rescue anybody over 20 MMSE”. That is now lowest the MMSE score that responds to an experimental drug. All late comers are treating those with average scores of MMSE scores 25 or ADAS-Cog11 15. As Alzheimer’s is neurodegenerative disease the relatively advanced disease can preclude a successful rescue of a patient or even possibility of stabilizing him. The other thing happening is massive outpouring of half-baked efficay data.

Here, we will strive to compare results from 3 companies $SAVA, $ANVS and $AVXL. Sometimes these are akin to oranges and sometimes apples and oranges.

The most fair comparision might be between $SAVA and $ANVS. Both treated MCI patients, the former up to 6 months the latter just 25 days. The narratives used by the companies differ but ultimatetly they are derived from the Amyloid plaque theory of AD. In my conviction both aim for limiting neuroinflammation notwithstanding their narratives. Though more widly touted, $SAVA presented less of improvement than the rapid results of $ANVS ANVS401. $SAVA over 6 months improved the patients cognition just by -1.6 ADAS-Cog11 points (negative values on this scale indicates improvement). Starting from similar conditions ANVS401 lowered the ADAS-Cog11 score by -3.3 in just 25 days (adjusted for placebo). In such short period of time the problem becomes the dispersion of the test data due to “statistical events” or chances of scoring higher even if the cognition objectively moves in any possible direction. The difference from initial condition was -4.4 ADAS-Cog11. The p-value went from p=.04 for initial scores to p=.13 indicating that some results could have been no different than the dispersion about placebo mean.

Let’s See How The Biomarkers Look for Both of Our Contenders

We can only directely compare A-beta42, Tau, p-Tau and YKL-40. If all those are undesirable then the winner hands down is $ANVS. ANVS401 pratically removes those from the brain. YKL-40 level indicates that neuroinflammation is practically gone. ANVS401 is supposed to lower the production of A-beta precursor APP by 60%. The mechanism of action has not been expained by $ANVS sufficiently well to come to definitive conclusions what the drug really does. Nevertheless is astoundingly effective in putting down neuroinflammation during the short span of time. I thought that all those drugs putting down inflammation will have middling results but ANVS401 does the real job on this front. This is compatible with the experiments conducted by one doctor who injected anti-inflammatory drug into neck portion of spine and the lowered the patients head down to have the drug migrate into the brain. The results were in just hours, with “fog lifting” as described by patients. Unfortunatelly, he was censured by FDA and videos were removed.

Looking into $AVXL and $ANVS as Synergistic Apples and Oranges

It is very hard to compare the above companies to $AVXL as it dosed the Middle and Moderate Alzheimer’s patients and not just MCI only. Nevertheless $AVXL scored great success with those who were on average MMSE = 23 or ADAS-Cog11 = 17. These aptients in just 5 weeks (35days) scored improvement of 1.2 MMSE or ADAS-Cogs11 -2.8, in 57 weeks this was 2 MMSE or ADAS-Cog11 -4.7 and finaly in 70 weeks 3 MMSE or ADAS-Cog11 -7.0.

ANVS401 shuts down neuroinflammation and Blarcamesine does on one hand the same but on the other hand it rejuvenates ( post [1] ) the neurons with possibly reversing the neurodegeneration described in post [2]. ANVS401 will probably have a quick action with a plateau whereas Blarcamesine will deliver consistent increases of cognition scores over longer period of time. These two drugs and will work in synergy.

$SAVA is no longer therapeutically relevant!

Bibliography

[1] SIGMAR1 Agonists – Therapeutic Swiss Army Knives $AVXL, Prilenia Therapeutics, $ATHA, $ALKS, $SAVA https://piotrpeterblog.com/2021/05/13/1372/

[2] https://piotrpeterblog.com/2021/03/05/novel-etiology-of-alzheimers-linked-to-neuronal-loss-of-function-due-to-changes-in-cellular-transcription-mechanism-and-dna-chromatin-complex-avxl-sava-atha-biib/