Replies to post #502192 on Anavex Life Sciences Corp (AVXL)

[Doc328]

The FDA has always been, and remains, flexible. They are open to many designs that could be discussed at end of phase 2 meeting. They even say "This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page" in the guidance.

showing flexibility:
Lecanemab phase 3 Clarity used CDR-SB at 18 months as primary endpoint. They also successfully hit secondary endpoints ADAS-Cog14 and ADCS-MCI-ADL (a related scale to ADCS-ADL - with some overlapping questions and some additional questions)

Donanemab used iADRS (which is a composite of ADAS-Cog and ADCS-iADL) ADCS-iADL are the instrumental questions from the full ADL scale and are more sensitive for MCI and mild AD patients. The data was also significant for ADAS-Cog13 and ADCS-iADL independently as well as CDR-SB(secondary endpoints)

Simufilam (failed) used ADAS-Cog12 and ADCS-ADL as co-primary endpoints

[boi568]

FDA Guidelines are not regulations and therefore allow for discretion. But they are also not nothing.

So, unlike with a regulation, a failed co-primary endpoint can still result in an approval so long as the Agency is able to use its scientific judgment to support the decision. In the case of an early AD trial, like the 2b/3, given the state of the science this approval possibility appears open in the case of a failed co-primary functional endpoint; on the other hand, I don't see how FDA discretion could be supported to ignore a failed cognitive co-primary endpoint. Even discretion has its limits, and can't tip over into "arbitrary and capricious" territory.

As I've consistently said, the use of the older FDA decisional guidance -- and the fact that other early AD applicants used it -- will complicate the path to an NDA approval for blarcamesine, but it will not necessarily block it.