I have read the entire EMA guidance for Alzheimer’s & the entire EMA guideline on the investigation for subgroups.
The reasons I assessed approval previously still stand and are to be presented in the re-eval (to be confirmed Tuesday).
- Pre-specified ABCLEAR1 to 144 weeks with exploratory ABCLEAR2 and ABCLEAR3. These subgroups show tiered benefit culminating in a functional cure. Mechanism/credibility of these subgroups is valid IMO.
- Effect on neurodegeneration alone should be approvable since no drug addresses this facet of this disease - also showed tiered improvement in the ABCLEAR subgroups.
- Safety improves in ABCLEAR subgroups.
- Think there is a case for CHMP/EMA to restrict indication to ABCLEAR1. Patients with mutated SIGMAR1 AND COL24A1 brought down the ITT and had worse safety. Will inquire into Anavex’s strategy going forward on Tuesday.
- Issues with trial size (or that there was only one trial) would not be fixable at a re-exam and therefore must not be the primary concerns for approval. Will ask about what ARE the concerns.
- Back to ABCLEAR3, this subgroup is inherently built of pre-specified ABCLEAR1 patients. ABCLEAR3 met all endpoints at 48-weeks. I believe this will be compelling - the weight of this data is certainly lower than ITT and pre-specified ABCLEAR1, but it’s highly significant, meaningful, and compelling.
- Oral delivery, cost, burden on medicare system, transportability all favorable for approval.
- Few other points but I’m off to the gym (ha)
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