Replies to post #508545 on Anavex Life Sciences Corp (AVXL)

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I get your reasoning, but there are two key distinctions between blarcamesine and the mAbs:

1. ABCLEAR3 is post-hoc, whereas the mAb subgroups (like APOE) were pre-specified and backed by full ITT efficacy plus strong A/T/N biomarkers.
For blarcamesine, the ITT clinical efficacy was modest, and the stronger effects only show up in the post-hoc ABCLEAR3 slice. Even within that subgroup, there is no established amyloid or tau biomarker effect. In contrast, the mAbs had also modest but clear ITT clinical efficacy and robust A/T/N signals across large, replicated trials. The APOE subgroup was used mainly for risk management, not to rescue efficacy. Their safety profile isn’t good, but it’s considered manageable with monitoring.

2. EMA has never approved a novel CNS drug before the FDA — and certainly not based on a post-hoc genetic subgroup.
Historically, the approval probability for a non-FDA-approved therapy using a post-hoc population is effectively 0%. Meanwhile, EMA’s approval rate for FDA-approved drugs is very high (>80%), and even higher when you include re-exam reversals. And yes, the two FDA-approved mAbs were ultimately approved by EMA as well. This rejection confirmed that EMA follows FDA’s lead, not leading, at least in CNS.