MayoMobile and Doc328 actually have a level of agreement on the chances of an accelerated approval after a successful readout of the 2b/3 AD trial. It doesn't look like it at first glance, but if you unpack an assumption or two, it will become clear.
Doc328: "Before the approval of Aduhelm, I had estimated the likelihood that A273 could be approved for AD with just one positive study (the 450 patient 2b/3) Now with the FDA approving Aduhelm with one positive study (n=1600) and one negative study based on biomarkers I will revise my estimates. . . . If clinical primary endpoint (ADAS-Cog) data is significant compared to placebo AND CSF [cerebrospinal fluid] analysis was performed on all patients and is significant for Ab42/40 ratios and/or Ab42/tau analysis improvements then the likelihood is much higher. So instead of 5%, I would estimate 50% chance of approval IF ADAS-Cog and CSF analysis (if on all or nearly all patients) is significant in A273's favor. There are still issues of smaller n and a less studied biomarker which is why it would not be 80-99%." (My emphasis.)
Powerwalker: "Doc, please remember the proof used by fda for its approval of adu* was based on the subset of 300 participants, not 1,600 as you claim. If one looked hard at the study, ~530 were on placebo and those getting the adu* was !1,070. Since only 300 showed any "results" of the drug working, 770 came up empty since that group was excluded from inclusion."
MayoMobile: "[T]he newly published PET imaging results, combined with preclinical and clinical Blarcamesine data lends great credence to the probability of Anavex holding a miracle drug capable of diffusing many central nervous system (and other) disorders. With this in mind, and combined with the potential for outright prevention, Anavex has a high chance of successfully marketing their drugs (2-73 and 3-71). Revenues earned by such a platform would certainly produce a top-tier biopharma with a market cap in the 100’s of billions."
Mayomobile: (In response to quantify) "I have a long list of reasons to support my thinking here, but I estimate a 92-97% chance of Alzheimer’s approval." (My emphasis.)
So we get two best case estimates of AD approval (MayoMobile is not explicit on AA, but it's implied) of 80-99% and 92-97%; these are really the same numbers expressed differently. The difference between the experts is that Doc328 holds fast to the FDA's commitment to the amyloid/tau theory and he does not credit the company's MOA, while MayoMobile trusts the efficacy of the Anavex Sigma-1 upstream MOA. There is a minor difference on the importance of the sample size of the 2b/3 AD trial, which I think will work itself out when clinical effect size is read out.
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