APOE3 alleles was never specified as an outcome measure.
APOE3 alleles may well be part of the P2b/3 pre-specified subgroup analysis co-variates as it was in the P2a post hoc analysis, but I doubt we would see APOE3 e3/e3 alleles as a PM selection criteria in new AD trials. That APOE3 e3/e3 allele carriers do a bit better is no surprise as their presence is known to lower AD risk and rate of decline. APOE3 genotype e3/e3 is fortunately also the most prevalent, which was also true in the P2a study.
As to:
So far the company has identified the WT vs the mutant type of APOE3 gene as a potential PM. Recently the company has dropped any references to that as a PM with Missling saying recently that all types of APOE respond at the high dose level.
I don't know where you got that from, but if you replace APOE3 with SIGMAR1 it sounds about right.
Anavex first identified the SIGMAR1 and COMT genes and variants of them as co-variantes of respons to A2-73. Since then COMT has gone on the backburner as having even less influence on A2-73 response than SIGMAR1.
The first presentation of KEM Analysis was at CTAD November 2017, the KEM concept was introduced i the September 2017 Corporate Presentation.
First time we saw a poster detailing the P2a AD KEM analysis was at AAIC 2018. The summary of that is also below and it identifies only SIGMAR1 and COMT gene variants as biomarkers of response to A2-73. Then in April 2020 we got the P2a data peer reviewed paper, which does not specifically mention APOE3.
Outcome Measures Go to sections Primary Outcome Measures : ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [ Time Frame: 48 weeks ] Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog)
ADCS-ADL (Activities of Daily Living) [ Time Frame: 48 weeks ] Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL)
Secondary Outcome Measures : CDR-SB (Clinical Dementia Rating Scale Sum of Boxes) [ Time Frame: 48 weeks ] Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared with placebo using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 48 weeks ] Assess the safety and tolerability of ANAVEX2-73 compared to placebo
Other Outcome Measures: Number of participants with change of brain volume assessed by MRI [ Time Frame: 48 weeks ] To evaluate the effect of ANAVEX2-73 on structural and Arterial Spin Labeling (ASL) MRI scan assessments characteristic for AD pathophysiology compared to placebo over a 48-week treatment duration
Blood assessment [ Time Frame: 48 weeks ] Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration
CSF assessment [ Time Frame: 48 weeks ] Changes in CSF parameters (Abeta40, Abeta42, T-tau, P-tau, NFL, YKL-40, neurogranin, BACE1 concentration) characteristic for AD pathophysiology from baseline and compared to placebo at
+48 weeks treatment differences within subgroups will be performed
Number of participants with pre-specified genetic variants [ Time Frame: 48 weeks ] AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed
RSCAQ sleep score [ Time Frame: Weeks 0, 4, 12, 24, 36, and 48 ] To evaluate whether ANAVEX2-73 improves sleep continuity as assessed on a serial basis (weeks 0, 4, 12, 24, 36, and 48) with a questionnaire that assess reported sleep continuity (RSCAQ)
Here is the summary from the from the 2018 AAIC poster.
Systematic analysis using KEM® identifies actionable parameters enabling a precision medicine approach to include best responders in follow-up Phase 2b/3 study • Patients with a wild-type SIGMAR1 gene were found to have an improved benefit from ANAVEX®2-73. Patients with a variant of the SIGMAR1 gene (rs1800866) were found to have a limited benefit from ANAVEX®2-73. Same for COMT variant (rs113895332/rs61143203) • Including patients with milder disease stage (baseline MMSE ≥20) and the exclusion of AD patients carrying SIGMAR1 variants results in a score improvement of +1.7 MMSE and +3.9 ADCS-ADL, respectively at week 57. The additional exclusion of the COMT variant results in a score improvement of +2 MMSE and +4.9 ADCS-ADL, respectively for the same period. Both effects would be clinically meaningful • The minority of the population (about 20%) has the variant SIGMAR1 gene, hence the majority of patients (about 80%) is expected to benefit from ANAVEX®2-73 • Gut microbiota has been collected and will be incorporated in future analysis • The data provides support to further clinical development of ANAVEX®2-73 and further clinical studies in other indications are planned or underway • Anavex is pioneering the use of precision medicine in CNS disorders, including Alzheimer’s disease
AI
Market Data 
Markets 
