Replies to post #466329 on Anavex Life Sciences Corp (AVXL)

[BAR123]

How come you don’t respond to your predictions about July 28th.

I forgot about his big prediction of massive volume on July 28 and the short interest going down to 11m shares and the stock price much lower. What happened there doc. Care to explain??

[Hosai]

This still doesn't show anywhere that 0.5 would correspond with the stage 3 mentioned. My guess is most of the 2b/3 trial would be somewhere between 2 and 3.
Also remember that it wasn't just ADAS COG passed also CDR SB with p value under 0.25.

Also there are paragraphs in the guidance that seem to water down the need for functional at stage 3 even if AVXL was mostly stage 3 under this interpretation -

"Therefore, FDA may consider other approaches, including endpoints based on cognitive assessments or surrogate endpoints, which may allow for shorter trial durations as a basis for approval in the earliest stages of AD (i.e., Stages 1, 2, and early 3)."

Patients with Stage 3 AD approaching the onset of overt dementia have relatively mild but noticeable impairments in their daily functioning. As patients have detectable cognitive and functional impairment at this stage of disease, it is important to demonstrate that a therapy favorably affects the observed impairments in both cognition and daily functioning. The independent assessment of daily function and cognitive effects remains an acceptable approach.
However, it is important to note that many of the assessment tools typically used to measure functional impairment in patients with later dementia stages of AD (Stages 4 through 6) may not be suitable for use in early AD patients. An integrated scale that adequately and meaningfully assesses independent effects on both daily function and cognition is also acceptable as a single primary efficacy outcome measure in early AD patients. FDA encourages the development of novel approaches to the integrated evaluation of subtle functional impairment that arise from early cognitive impairment (e.g., facility with financial transactions, adequacy of social conversation).

In early Stage 3 AD (which may be difficult to distinguish from late Stage 2 AD), FDA will consider strong justifications that a persuasive effect on cognition as measured by sensitive neuropsychological tests may provide adequate support for a marketing approval. It would generally be expected that such effects on cognitive measures would be supported by similarly persuasive effects on the characteristic pathophysiological changes of AD, and positive trends on functional outcome assessments. As previously described, a time-to-event analysis approach could also be considered (see section IV. B.). Whether effects on cognitive outcome measures would, in the absence of a meaningful change in function, support either traditional or accelerated approval would require detailed discussion with the Agency."

[sab63090]

Dox328...thanks!
I don't qualify to judge because all of this is way above my head, but I do consider you to be more informed than most who post here...

I did notice some problems with "Conflicts of Interest" especially for fees names like Acadia, Biogen, Elsai, and grants from those names and others

Conflict of interest statement
AP reports personal fees from Acadia Pharmaceuticals, Alzheon, Avanir, Biogen, Cadent Therapeutics, Eisai, Functional Neuromodulation, MapLight Therapeutics, Premier Healthcare Solutions, Sunovion, and Syneos; grants from Alector, Athira, Avanir, Biogen, Biohaven, Eisai, Eli Lilly, Genentech/Roche, and Vaccinex. RI has nothing to disclose. MS reports personal fees from Alzheon, Athira, Biogen, Cortexyme, Danone, Neurotrope, Regeneron, Roche-Genentech, and Stage 2 Innovations; stock options from Brain Health Inc, NeuroReserve, NeuroTau, Neurotrope, Optimal Cognitive Health Company, uMethod Health, and Versanum Inc. Additionally, he has intellectual property rights with Harper Collins. SK and IR report employment with Biogen.

[12x]

Here is how ChatGPT answered my questions on mapping the FDA AD Stage to CDR/MMSE. Based on ChatGPT, the FDA Stage 2 to CDR-0.5, Stage 3 to CDR-1.0, Stage 4 to CDR-2.0, and Stage 5-6 to CDR-3.0. The CG also maps FDA Stage 1-3 to MMSE >20. The ChatGPT seems to agree with the p2b/3 trial patients being FDA-defined Stage 1-3 (early AD).





For MMSE mapping: