This post isn’t to sugarcoat the pending rejection of Anavex’s marketing application – what happened today is unfortunate, and while I don’t like to comment on the SP, the drop is obviously painful for many.
I did want to share my thoughts going forward.
These events are a steppingstone, not a roadblock.
Admittedly, most of my focus has been on science and drug feasibility. It always has been, and I have been forced to investigate regulatory processes considering these updates.
Anavex was asked to file by the EMA despite the absence of certain OLE data (partial 144 week data was included), ADNI comparisons, and GWAS. The EMA deemed the application at that time strong enough for possible approval (as it does with many companies, some of which are rejected despite the invitation to file).
Data that came out after the application (ABCLEAR 2, ABCLEAR 3, Brain atrophy TIED to ABCLEAR2/3, ADNI comparisons, prodromal comparisons, etc.) were ALL excluded from the actual regulatory decision. The company is almost certainly going to appeal as soon as possible (in Dec) to try again with approval. The difference is that with appeal, they CAN use all the aforementioned data which insurmountably improves the strength of the filing, with all that information now able to be officially considered by the CHMP. This process is 15 days for the company to appeal, 60 days to give new data, 60 days for CHMP to give new opinion.
This process is eerily similar to what happened with the monoclonal antibodies in Europe, being approved after an initial rejection. Without getting into details, it is probable the decision today was not unanimous, and it’s a matter of bringing a few more panelists in favor of approval – which would seemingly be easy with ABCLEAR3 data considerations.
I have been invited back as an analyst for the next conference call. Some of my questions will be:
1. Can you please confirm that ABCLEAR3 data will be a part of the appeal process
2. What is your strategy going forward for approval, are you going to try for full approval, accept CMA, and/or perhaps narrow indication to just ABCLEAR3 patients – what do you hope to be approved realistically with the appeal and feedback you’ve received already
3. Can you give color on the feedback given during the oral explanation and review so far
4. For your imminent FDA meeting, are/did you discuss acceleration or special vouchers – perhaps for ABCLEAR3 narrowed indication only [the nice thing about waiting for FDA is that unlike the EMA application, the FDA application will include ALL data presented up front. All of the ABCLEAR data, ADNI, etc. therefore it may be feasible for the FDA to accelerate ABCLEAR3 as it is a functional cure for >50% of the population]
To close out, with what we now know regarding the regulatory process and which data was omitted from this decision, it seems plausible (if not likely) that the company will still walk away with an approval upon appeal. Perhaps an appeal was always in the plan, with an approval in Nov being a possibility but non-likelihood – I do not have insights into this strategy. In all cases, Anavex will be appealing, they will be providing new data for regulators, and all signs still point to an eventual approval. Efficacy with ABCLEAR 1/2/3 was all improved over ITT. ABCLEAR 2/3 especially saw significant improvements to cognition and function, and these improvements were confirmed with extra benefit to neurodegenerative biomarkers and amyloid reduction. Patients with these favorable genomes far outpaced monoclonal antibody improvements, saw improved safety profiles, and were essentially gifted a functional cure. As I have mentioned before, it is irrational for regulators to not approve Blarcamesine – at LEAST for ABCLEAR3, with possible conditions for other subgroups.
Wishing you well while you navigate your next steps with this investment. It has been a very long time, but I still see the end of the road, and I personally will not be selling here with resolve the company will get their approval. Manage risk accordingly.
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