Replies to post #413082 on Anavex Life Sciences Corp (AVXL)

[Doc328]

However, can you play devil's advocate and assume that Dr. Missling is correct that both endpoints have been met...and give us the best possible scenario that would validate Dr. Missling's claim?

Playing Devil's advocate to one's position is important in any investment. I don't believe that the AD trial hit the coprimary endpoints. I was concerned about that after CTAD and more sure after the Dec 2 Monday morning conference that obfuscated the poorly delivered TLD even further (prompting sale of almost all shares upon market open). One thing that really bothered me was Missling's interchanging outcomes and endpoints as though they are the same thing.

In this contest, how could the actual results validate Missling's claim of meeting the endpoints? We do not have the AD trial's SAP and if it leads to a phase 3 trial, it likely will never be available. This link is to one of the Aducanumab trial's SAP. Although results of teh study were not impressive and the FDA should not have approved it, they did publish their SAP and it a well written example that can put Missling's claims in perspective. If you look at page 19 (Table 2) you will see that they had the primary analysis: difference of means change from baseline at 78 weeks - data was imputed with MMRM MAR and analyzed as the primary endpoint (this became either the success or failure determination for the entire study). Then they re-analyzed with several other imputation methods (sensitivity analysis which highlights the robustness of the data vs just lucking out with choice of imputation). Then they did supplementary analysis (including responder linear regression odds ratio). I have assumed since CTAD and given the results that the Anavex AD trial 'hit' with a a supplementary analysis but not with the primary analysis -- hence it 'missed' overall. I believe this is Missling's out as far as his statements but it won't pass muster with the regulatory agencies