Replies to post #257367 on Anavex Life Sciences Corp (AVXL)

[anders2211]

To me, it is becoming more apparent that a phase 3 for PDD is needed only focused on Group 1 from you chart. That will not bode well on the SP I suspect.

[RedShoulder]

"As far as I am aware the stratification to include the APOE3 alleles has not been mentioned in any previous presentations from Anavex. The only difference between Group 1 and 2 is the APOE3 alleles, which appears to make a very significant difference to response, much more so than the SIGMAR1 and COMT variants vs. wild type analysis."

Investor2014, thanks for your reply and link.

https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12013

[Doc328]

ApoE4 status was found to be an important covariate to the response for MMSE and ADCS-ADL changes in the Hampel CTAD 2018 presentation (look at slides 16 and 17)

Sigma-1R variant and COMT variant were found to be covariates to the subjective ADCS-ADL but not for the objective MMSE (same slides)

Though probably just an oversight by TGD and his team, the Oct 2019 presentation has very similar slides (slides 19 and 20). On those, ApoE4 was not listed as a covariate for the 2 measures despite mentioning that it was looked at in the small print.

Interesting in the recent Hampel paper, another genetic marker HLADRB1 also had borderline significance for the slope of MMSE but not the delta. This is one of the major histocompatability complex genes and has a role in antigen presentation. Some alleles are associated with a higher risk of MS or RA.

My interpretation of the significance of the genetic markers are: ApoE > S1R > COMT > HLADRB1 .

ApoE4 is over-represented in AD, and to a lesser extent in PDD. In AD, patients who are ApoE4 (E4/E3 or E4/E4) progress, on average, faster than those who are E3/E3. E3/E3 is the most common in human population butE4/E3 is actually the most common in AD. Only one patient had one E2 allele so E2 is excluded from any analysis. Patients who express the S1R Q2P variant and also have ApoE4 progress even faster than those who just have E4 (so patients not expressing these likely progress slower than average). link

The KEM Analysis approach is great, but to me it is a concern that we only have these findings in such a small trial that we end up with subgroups consisting of 2 patients.

To me, too. I look forward to the AD 2b/3 study.