Replies to post #495952 on Anavex Life Sciences Corp (AVXL)

[Steady_T]

Doc, It is my understanding that many CNS drugs work only on a less than 50% of the population. Is that correct or do I have bad info on that?

[12x]

So by emphasizing the wild type that admit no long term significant effect on the variant

This is the point I tried to raise earlier, but it seems that few here fully appreciate the implications.

The new AAIC/PR data show that at 192 weeks, the ABCLEAR2 subgroup had an ADCS-ADL mean difference of +9.50, while the overall ITT population was only +4.30.

Given that ABCLEAR2 makes up 65% of the p2b/3 trial population, simple math suggests the non-ABCLEAR2 subgroup actually declined by -5.36 points on ADCS-ADL — meaning they did worse with early-start treatment than with delayed treatment.

If this holds, it’s hard to imagine CHMP granting full approval to a drug that appears to harm (or ineffective) a specific genetic subgroup. That’s why, based on this data, I now see full approval as highly unlikely.

That said, I’m not bearish — quite the opposite. Strong efficacy in a well-defined 70% genetic responder subgroup is arguably more compelling (and approvable) than a mediocre effect across the full population. It makes a strong case for precision-labeled approval or even conditional marketing authorization (CMA). Had the 48-week ABCLEAR2 subgroup be Stat Sig, the precision-labeled approval would have been a done deal.