Replies to post #475825 on Anavex Life Sciences Corp (AVXL)

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For LEQEMBI (lecanemab), APOE-related safety analyses were predefined, as the potential for ARIA-E (amyloid-related imaging abnormalities with edema) and ARIA-H (hemorrhages) in ApoE4 carriers is a well-documented safety concern in anti-amyloid antibody trials. These analyses aimed to evaluate and mitigate the risk in this subgroup.

Regarding efficacy: APOE subgroup efficacy analyses were also predefined, not post-hoc. The Phase 3 CLARITY AD trial specified subgroup analyses to examine treatment effects across ApoE genotypes (e.g., carriers versus non-carriers) as part of the study's statistical analysis plan (SAP). This is consistent with standard practices in Alzheimer’s trials, where stratification by ApoE genotype is often included due to its known influence on disease progression and response to treatment.

Thus, both safety and efficacy analyses for the APOE subgroup in LEQEMBI's trials were planned in advance and were part of the pre-specified analyses submitted to regulators like the FDA and EMA.