Replies to post #508521 on Anavex Life Sciences Corp (AVXL)

[Doc328]

how do you think CHMP interprets this?

I think they are much less concerned about MOA than this board is. What they care about is safety and efficacy. So bottom line would be does the single small short term 2b/3 with higher than typical dropout pass the threshold of efficacy? If not is biomarker data compelling enough to overcome this deficit? If no and no, drug will be denied.

I ran some calc's when Anavex submitted the MAA in 2024 (did not post) to determine whether I should significantly enlarge my small position. My thinking had been a second trial is necessary and I wanted to re-evaluate. Doing a Bayesian analysis of whether a second trial would absolutely (or at lest 96% absolute) be needed I started with a prior probability of 5% (success of AD drugs in general) and using the ADAS-Cog only of p=0.02 I came to a posterior probability of 20% or as high as 45% if the power of the trial was truly 80% (which in retrospect would have been generous given the actual delta response and higher than expected variance inthe endpoints). If the CHMP was to run similar quick calculations there would be a very low (say 4%) chance of approval on one study if they felt (as I do) the odds of the drug actually working was 20-45%. If a second trial also showed p=0.02 and we develop a new posterior probability based on the 20-45% range using a trial powered 80% and p=0.02 gives a likelihood of the drug actually working to be 80-93% --- throw in some biomarker success and the drug is approved. A couple of needed if's but this is the new bull thesis.

Missling has poorly powered every single trial that Anavex has done, likely trying to save money but probably more a character flaw believing his magical thoughts of success (best case) vs typical case. This is apparent in his publication detailing how he underpowered the Rett trial (they even used Bayesian stats! but had wrong assumptions - garbage in garbage out) https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15843

One can hope that Dr. Jin will design the phase 3 that will be required before submission and that Missling and his 2 BOD cronies will be gone soon. .