Replies to post #504956 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

Sure, but interested in concluding with certainty whether or not claims that the EMA 'doesn't care about' the ADCS-ADL co-primary endpoint miss and the assumption that the CDR-SB secondary functional endpoint under the multiplicity rule can replace it (assuming in the SAP hierarchy where it needs to be).

To me that is the top crunch factor for any form of approval - don't give much weight to any of the OLE and post hoc hypothesis peer reviewed on not. All those will IMO need a well designed RCT to verify, which is why CMA is most likely for an approval outcome.

[frrol]

The rapporteurs nominated by the CHMP will be assessing, independently of the company, our study populations. Among other things, they'll be looking at the P2b/3 disease status, and also the overall prospect of survivorship bias in the OLE. We can't be confident in Missling's opinion obviously but Jin and Talavera are possibly more credible. I certainly hope so, as an investor. Let's see if we get passed the LOI.

[sab63090]

Thanks, Doc328.....you also provide updates that should be seriously considered by all here!

Steve

[boi568]

"Actually Dr. Sabbagh (and the FDA guidance) considers stage 3 to be MCI and stage 4 to be mild AD. The 2b/3 was about 60% MCI (CDR 0.5) and 40% Mild AD. This is one reason why the 'ADCS-ADL not needed with recent guidance' is a silly argument.'

Per the most recent Timo Grimmer Anavex presentation (slide 15), the 2b/3 trial eligibility criteria included "Met the NIA-AA 2011 criteria for diagnosis of early-stage mild dementia or MCI due to AD."

https://www.anavex.com/_files/ugd/191fc6_491124ecec494857b5d656917feda594.pdf

The EMA accepted the NIA-AA criteria "for diagnosis of AD for research purposes and for trial enrichment" in 2018 Guideline on the clinical investigations of medicines for the treatment of Alzheimer's disease. See Introduction at page 5:

https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicines-treatment-alzheimers-disease-revision-2_en.pdf

Nothing silly about these documents. And Anavex's application is presently being considered by the EMA, not the FDA, so the EMA position on what is "early AD" is what's relevant here.

I'll also note that the last time you posted about the 2b/3's MCI to population percentage, you described it as 65 percent: "Prodromal is CDR-G 0.5 (clearly spelt out in reference 3 of the PR). This is commonly referred to Mild cognitive impairment, not normal aging. In the 2b/3, 65% of the treated patients in the 2b/3 were CDR-G of 0.5."

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