Anavex Life Sciences Corp (AVXL)

[Joseph_K]

Thanks for the reply. :)

She wasn't talking about primary versus secondary. She was talking about when a SAP lists various ways to statistically test a single endpoint. Specifically, we were talking about relying on an Odds Ratio as an alternative statistical approach to using a difference-of-the-means approach. Sometimes sponsors pre-specify multiple approaches. One reason for that, I think she said, is that the alternative tests can be helpful for getting the FDA to permit a broader label (though I don't know how that works). The other reason is that if the first-listed test doesn't have an adequate p-value, success on the alternative (lower-weighted) tests can still bolster the chance of approval in an otherwise promising trial. She's 100% certain that difference of means was first-listed in the SAP (maybe I could have bargained her down to 99% if I'd tried? :) ), but she does think that the Odds Ratio, depending on the actual, so-far-not-revealed numbers and on whether the thresholds were pre-specified, could be helpful since the other two major endpoints were met. Even with the two 0.025 p-values, she says hitting all three of the primary and secondary endpoints, even with higher (but sub-0.05) p-values would have made a stronger case; but she agrees that the two-of-three 0.025s can be a legitimate basis for calling the trial a success.

The whole approval process is a sort of sliding scale as I've come to understand it. It isn't like two p-values < 0.025, or even three p-values < 0.05, means you get approval; approval is based on the totality of results and other factors. I'm about positive that all endpoints were not met (unless one counts a fudged claim that succeeding on an alternative test -- Odds Ratio in this case -- means an endpoint was met, when conventionally it does not mean that), but I'm quite optimistic about approval. I combine the two 0.025s, hopefully bolstered by the ADL Odds Ratio (and, for that matter, by the ADAS-Cog Odds Ratio if the actual numbers are good), the safety profile, ease of administration, the probable price (given weight by the EMA), and the widespread social need and current pathetic standard of care, and think the chances are very good (even if they would have been even better had all three endpoints been met ;) ).