Anavex Life Sciences Corp (AVXL)

[OFP]

Wow...forgive me if I can't match your prolific writing. I'll try to address the points though.

Your point is that Anavex “super responders” don’t mean anything because Myriad Genetics also had them in their phase 2 trial. The evidence that I can find does not seem to indicate that Myriad Genetics had “super-responders”

I'm not sure how you are defining this. I called them "responders" not "super responders" because that is a AVXL term and it did not seem direct comparisons could be made in terms of degree of effect from F1ash's excerpts. However, I think we can be pretty certain that 2-73 will not meet the "42% of Patients on Flurizan™ Had Improved or Not Declined After 24 Months" standard.


I won't try to defend Myriad's subgroup analysis as that is always fraught with peril but as far as subgroups go their mild AD results were pretty intriguing and there is no reason to say they are incongruent because moderate AD should have shown a stronger effect. Many theories might have explained such a pattern.

All of Anavex’s results were congruent and complimentary. For example: Low-High dose was statistically significant to affect MMSE-delta and ERP-delta scores with MMSE-delta (p=0.0285) and ERP-delta (p=0.0168), respectively.

Given the subsequent decline I really don't think part A results have any relevance. This is an analysis of the tiny up-blip seen with any treatment (including placebo) followed by a subsequent down trend worse than or equal to placebo. Patients were treated for only a part of that 5 weeks and absolutely no details have been provided on the methods of statistical analysis dealing with the varying oral/iv doses, potentially even before they knew the oral bioavailability.

Quote: “Computerized versions can somewhat limit bias however I think you confused the Cogstate tests with MMSE and P300 when you wrote this. The MMSE requires human assessment/scoring.”

No, you are confused between modern versions of the cogstate tests and those such as Myriad Genetics used. Myriad Genetics used a MMSE that indeed was assessed/scored by humans. Anavex uses more modern cognitive tests that are computerized.

Even the wording here is confused. The MMSE is not a Cogstate test...the Cogstate tests are the computerized ones. If you've ever performed a MMSE you'd know how difficult it would be to put on a computer (verbal, writing, performance tasks...many of which are open ended and patient specific). When I've heard AVXL refer to their computerized tests they were always talking about the Cogstate battery.

LOL. You didn’t read the response last time. The reason that the P300 amplitude was not in the past correlated to drug effect is that no previous drug stsignificantly improved the underlying “health” of neurons. Given how A2-73 works, should there be any major change in latency.

I did read your response the prior time and I still disagree with it. I know a fair amount about the P300 and I don't think you are going to characterize it well with one or two references. Like almost all evoked potentials the amplitude of the response is far more variable than the latency. As a result, very few amplitude measures are applied across populations while latencies are most useful. As you know, there actually are drugs that improve AD and these effects have been correlated to latency but not amplitude. If one wanted to use amplitude as a measure it would not make sense to do it the way AVXL did...they took a pooled grand average. If you want to minimize the variability of amplitude you would compare each patient to themselves not a grand average. So AVXL decided to only report the less useful parameter and analyzed it in a suboptimal way....hmmmm.