Anavex Life Sciences Corp (AVXL)

[Joseph_K]

I'll expand on Investor's reply. By your logic (a not unreasonable belt-and-suspenders approach to seeking approval), it would be smart for everyone to request AA designation for every NDA. While the percentage of AA requests has increased in recent years*, it's still a minority of total NDAs. To me, applying for AA indicates some degree of lack of confidence in the results for the primary and secondary outcome measures. If they were slam dunks, Anavex would not bother with AA, which has its downsides, including more time and effort to prepare the NDA, the extra trial, the conditioned approval.

While the TLR claimed that endpoints were met, it fell short of including the standard support for that claim, which is weird. My belief is that there may be, or perhaps likely is, data that arguably supports the claim, but at this point I'd be very surprised to learn that the data robustly and unequivocally supports it through standard measures. If the results had been that robust and clear, we wouldn't be hearing about AA, and the expected summary of those results would have been in the original TLR or added shortly after the CTAD rush.

I also think it's possible that the results may have been okay-but-not-great and Anavex is concerned the FDA will want a larger and longer confirmatory trial. Our trial had about 500 patients and ran for 48 weeks. The big lecanemab trial had about 1800 patients and ran for 18 months. Lilly's Phase 2 for Donanemab had 272 patients and ran for 72 weeks; and its upcoming Phase 3 will have 1500 patients and "duration including screening and follow-up is up to 93 weeks."

My belief is that the size and duration of the P2b/3 might have been adequate had the results been wonderfully clear and convincing but not adequate for results that were just okay. I don't in the slightest blame Missling for the trial size and duration; Anavex doesn't have BP's financial resources, and I think he did a great job in light of that. But the FDA may want a not-shoestring confirmatory trial.

This theory (okay-but-not-great results from a relatively small, short trial requiring a bigger, longer confirmatory trial), could, IMO, be the basis for a non-PM confirmatory trial. Investor may be right that the next trial will be Precision Medicine, but I believe my theory for a possible non-PM trial is plausible, and we can't guess well between the possibilities without knowing more. If the theory is correct, and the surrogate biomarker evidence is good, we'd be on our way to getting 2-73 to the Alzheimer's market "relatively soon" (well before another trial is completed) while not limiting the population it can treat.


* "A higher percentage of novel drugs continued to use the Accelerated Approval pathway in 2021, according to the report, with 14 of 50 drugs (28%) using the pathway. In contrast, 12 of 53 drugs (22.6%) in 2020, 9 of 48 drugs (18.7%) in 2019, and 4 of 59 drugs (6.7%) in 2018 received the Accelerated Approval designation."
https://www.raps.org/news-and-articles/news-articles/2022/1/fda-approved-more-first-in-class-drugs-more-with-a