Anavex Life Sciences Corp (AVXL)

[boi568]

This is an interesting ADL discussion from a statistical standpoint, but it's really a transposed version of the argument that "because the 2b/3 failed the ADL co-primary endpoint, the regulatory agencies are unlikely to approve an application."

This is not how policy is applied. As far as we can tell, the EMA as a matter of policy does not require the ADL co-primary endpoint for early AD, and the FDA is well on the road to the same place. (Anavex 2024 CTAD slide note; FDA draft guidance.)

Policies need to be reasonable, but they are necessarily somewhat blunt instruments. There is always an occasional instance where you can pretty easily argue against a policy on the merits. For the sake of argument, perhaps this is one of those times -- perhaps. It wouldn't be the case that the EMA, say, would now need to make a policy exception to allow for an approval because of the stats; it's the reverse, the EMA would need to make a policy exception to justify a disapproval.

When you argue that a trial has failed for regulatory purposes for missing an unnecessary co-primary endpoint (even though it fully met the required regulatory primary endpoint), you have lost the plot. It's comparable to the circumstance where a heavy underdog in a sport easily beats the spread and loses, achieving a "moral victory." That's something to feel good about, but it was still a loss. Flip it, and here's a circumstance where we you have a win -- an approval -- but there's something to feel bad about. It's still a win.

What matters is what the regulators want to see at the time they make an approval/disapproval call, not what they or the applicant wanted to see a few years before when the trial was designed.

In other words, it will be an uphill battle here to argue that the 2b/3 trial failed under the terms the EMA uses today. You can argue that it failed on its own terms, or that the EMA's terms are wrong. Both interesting arguments -- to a point -- but irrelevant and a waste of time. The EMA knows how to apply its own regulatory standards, and if it has accepted the argument that the 2b/3 had failed because the ADL co-primary endpoint was not hit, the CHMP would never have green lit Anavex submitting an MAA. Full stop.