Anavex Life Sciences Corp (AVXL)

[lifescienceDD]

Doc328 is a reasonable voice of sanity. It would benefit us to read through his comments.

Yes, this is an issue on ADAS-COG. Even if I give AVXL an extra boost by using all patients enrolled (n=170 vs. n=338 pooled, again this is BENEFITTING AVXL with more N than using a smaller ITT # which they did not disclose) and plug in the direct #s of 4.11 (0.86 SEM) and 2.26 (0.51 SEM), I get 2-sided p>0.05. I encouraging everyone on this board to take 10 seconds and do it yourself - https://www.graphpad.com/quickcalcs/ttest1/?format=SEM. Plug in n=170, 4.11 with 0.86 SEM vs. n=338 pooled, 2.26 with 0.51 SEM from Slide 21. Yet somehow AVXL legal team greenlighted press releasing "MET PRIMARY AND KEY SECONDARY ENDPOINTS".

The problem with A273 is that it looks like the main cognitive data did not pass the one sided 0.25 (or two sided 0.05) threshold. And that was with a very liberal modified ITT first ignoring patients unable to get titrated to enter the maintenance phase and then excluding patients who did not have a 48 week measure .

Yes, exactly. It is mindnumbingly bizarre that the two pre-specified primary analyses from the CRO were the first things AVXL received (and AVXL has already shown us one of them on ADAS-COG), but is withholding the ADCS-ADL mean difference.

We don't even know the ADCS-ADL mean change.

I have given AVXL the benefit of doubt that pooling is acceptable (pooling can only help a a sponsor because it gives you increasing powering) and that they can present 30/50mg N splits later. Even with pooling, I came to the same conclusion as you.

Was the pooled data the pre-specified cohort in the SAP? If so, the analysis to date is ok to present as the cohort though insufficient for an NDA (IMO) (due to one sided > 0.025 and lack of co-primary ADCS-ADL mean change data).

Amen, I have zero clue why on earth N was not disclosed. I encourage anyone to give an example of a P3 pivotal readout where N for an analysis was not spelled out.

Why was n not included in the clinical endpoint slides?

I'll go even further - folks on this board liberally talk about a surrogate biomarker for AA for 2-73. Aduhelm (via ab plaques) and Sarepta (via % dystrophin) are clearly linked to the biological mechanism of action so it was straightforward to at least make the case for their biomarkers. Why hasn't anyone on this board pointed out an AA biomarker for 2-73 yet? It should have been prospectively identified like these two examples.

So I put the likelihood at near zero. I do think you came up with possibilities that together add up to the 1-2% chance that I give for AA

I look forward to PDD/Rett's updates to help us shareholders out in the coming year. But this lack of disclosure on the most basic pieces of the AD trial perplexes me.