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!
Alzheimer’s trial as widow makers
Dr Missling by choosing to have only 32 patients in Alzheimer’s phase2a proved that he was very conservative with company’s resources and not overly enthusiastic about ANAVEX2-73 prospects. Ask questions first, shoot later. The run up to $14 on hopes of “quick cure”=”quick riches” was indeed a disappointment to shareholder or speculators (not much I think, at least to the experienced ones) in $AVXL stock. On the other hand Dr. Missling tactics of incorporating genetics, Ariana’s AI, microbiota and ingenuous financing, just to mention few, are a proof of strategy aiming to build lasting value.
The Parkinson’s Dementia Disease study phase2 has about 44 patients per cohort. By looking back, one can see that the initial miserly 32 subject spread over 3 cohorts dwindled to 9 patients in High Concentration Cohort who could be used to prove the hypothesis of ANAVEX2-73 efficacy, but they were too few to do it outright, they did it over span of few years. When looking at the PDD trial phase 2 every cohort has ample number of participants to end up with at least ~30 patients needed for minimal sample in life sciences. This alone suggests that Dr. Missling as much as trying to economize on sample size has now full confidence in Blarcamesine. Remember, for 20 or so years 95% of trails for Alzheimer’s drugs ended up as failures, making AD a proverbial widow maker. I guess that on 9 patients in High Concentration cohort you can discount any chances on an approval or partnership in the world so intensely afflicted with bipolar disorder of hype, dashed hope and failure. The bipolar condition afflict the small companies to a greater degree than the Big Pharma companies, who are more observers than actors in this field. Though those who speculate bet more on Big Pharma. However strong the signal was in AD Phase2a most of the people in the field plus the pundits were skeptical as “great discoveries” can be had a dozen at a time and even cheaper a 2 years later.
Let us go over in details why and how PDD phase 2 is relevant for Blarcamesine and $AVXL.
- Duration of trial: 14 weeks. In AD Phase 2a the patients who responded positively to ANAVEX2-73 did it over period of 7 week in very rapid fashion and then they split into one group slowly improving and one slowly descending in their MMSE scores. Repeating this pattern in 14 weeks would corroborate AD Phase2a with at most 44 patients and had it been weighted statistically as significant when seeing the same strength of the signal this would be complete. The therapeutic result can even be greater as Dr Missling pointed out that even the 30 mg cohort responded.
- The use of Cognitive Drug Research Computerized Assesment System Continuining Attension measurest among others reaction time both in mental aspects as well as motor skills. Nice name comes here to mind, psychomotor. Wikiepedia pages lists the know etiology of Parkinson’s:
The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of proteins into Lewy bodies in the neurons. So another undetermined primary cause neurodegenerative disease with the most conspicuous cause (dopamine deficiency) and neuron death located in one region due to homeostasis deregulation spreading from origin to Lewy bodies in particular. Is Lewy Bodies Dementia next target? This is kind of like a cross between AD and Rett. On conceptual level only.
- If CDR-CA would measure the amount of rescue extended to motor neurons on global level, just beyond pure dopamine deficiency, at least in the context of Blarcamesine study, anti-neurodegenerative properties of Blarcamesine would be buttressed. CDR-CA was also validated as a measure in AD. Dr Missling mentioned that notable strong signal was detected in memory measurement. If response in psychomotor skills would be statistically significant and would be better or equal to the existing therapy, we have killed two birds with one stone. This is another evident reason to think of ANVEX2-73 as neuronal broad-base homeostasis drug than one working on one single chemical reaction in a cascade like most of the old guard drugs do, or SOC.
- Members of the Ariana team are co-authors of the presentation. Are we again pursuing the genetic signature of perfect PDD patient? I am not a scientist so I do not know a lot of details about the genetics of the disease. The approach taken by $AVXL is not to only concentrate to bring the drug to trial but to create knowledge base so that a drug like ANVEX2-73 can be assured to beat all possible ways FDA can find to make life difficult to $AVXL. Dr. Missling creates a franchise not just a one wonder-drug company.
- PDD phase2 with very brief exposure of just 14 weeks corroborates AD Phase2a the exploratory trial. I called AD Phase2a “exploratory” because with the least of money Dr Missling was trying to find out whether there is anything in the AD field for $AVXL. The extremely low number (in absolute terms) of very strong responders determined the way forward without destroying the company financially. The penalty is time. I don’t think that anybody in FDA would risk giving, even at this junction, green light for approval without a partnership; a foot into the door of the club.
- The coming Rett results and PDD Phase2 results to be broadcasted at CTAD 2020 in Boston validate the attractiveness of $AVXL to join with Big Pharma company in partnership, or rather they quicken the time for it. On how Dr. Missling will play this out will depend the future of the company.
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