Replies to post #467124 on Anavex Life Sciences Corp (AVXL)

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What Soumit is concerned about the dose dependency was not confirmed in P2b/3. Among the 4 measures, 50mg has better efficacy than 30mg on ADAS-Cog13 (2.149 vs 1.934) and CGI-I (0.314 vs 0.248) but 30mg has better efficacy than 50mg on CDR-SB (0.502 vs 0.465), and ADCS-ADL (0.89 vs 0.652). CM argued the dose-response is confirmed in the phase 2A trial. I don't believe regulators will accept the 10-person cohort trial as confirmation. Then question is short of another trial, is there anything from OLE that can be used as dose dependency confirmation?

If the 126 placebo completers (along with the 107 30mg completers) were titrated using the new method to 50mg in OLE, we might have a second chance to demonstrate the new titration can reduce dropouts and more importantly, to show halting of disease progression at 50mg (aka high concentration).

[color=red]So it was a bit higher than the 30 milligram group, but not by much. So they're pretty much close, and that's why I also prespecified the two arms together against placebo in a predefined analysis[/color]. So that was the background. So we have seen prior to that a dose response curve in our Phase 2A. So there's no doubt about the dose response is confirmed. But what we now notice is that in this trial where we and that's coming to the second part of the question, where we noticed where we force patients to uptake trait to the target dose 50 very quickly within two weeks and then to three weeks, we noticed that didn't -- was very well received.