Replies to post #429259 on Anavex Life Sciences Corp (AVXL)

[kevindenver]

I said nothing about endpoints. you did. I said "maybe $AVXL will release results for all of the measures? RSBQ, CGI-I, and an anchored score."

Also I was responding to your AUC ramble and looking forward not backward.

With this much time gone by maybe $AVXL will release results for all of the measures? RSBQ, CGI-I, and an anchored score. I like the anchored score idea because it just seems to make sense and I think the FDA will appreciate the effort. In fact so much so it will be used for future studies in Rett Syndrome. And for the topic at hand regarding the use of AUC it will be a footnote specific the the study it was used in

[12x]

Anavex has issued not only 1 but 2 PRs in June to confirm RSBQ and CGI-I as co-primary endpoints. See below. Between June and August 13 ct.gov update, there was plenty of time for Anavex to communicate the endpoint change to CRO. What happened?

Here is the EXCELLENCE timeline:

9/22/22 clinical.gov updated (moved RSBQ to primary and CGI-I to secondary)

2/2/23 company PR enrollment completed but didn’t provide endpoint update. . “In communication with the FDA, we received their input on the endpoints, which were utilized in this study.”

2/7/23 Q1 23 CC, BGIT confirmed with Missling “no AUC”

6/6/23 company first time PR RSBQ and CGI-I as co-primary endpoints

In communication with the FDA, the Company received the Agency’s input on the study endpoints, which were utilized in this clinical study. The Rett Syndrome Behavior Questionnaire (RBSQ) total score and Clinical Global Impression Improvement Scale (CGI-I) score are co-primary endpoints in the statistical analysis plan with specified linear mixed-effects models for repeated measures (MMRM) as the primary analysis methods.”

6/13/23 company for the second time, PR RSBQ and CGI-I as co-primary endpoints

In the EXCELLENCE Phase 2/3 ANAVEX®2-73-RS-003 Rett syndrome pediatric clinical trial, the characterized Rett Syndrome Behaviour Questionnaire (RBSQ), together with the Clinical GlobalImpression Improvement Scale (CGI-I), represent the co-primary efficacy endpoints of the study.


6/28/23 PR us Rett extension Not sure what to make of this PR. Incoherent statements. Hard to conclude whether there were improvement from week 7 to week 12.

The effect of ANAVEX®2-73 (blarcamesine) in the double-blind part of the U.S. ANAVEX®2-73-RS-001 study was maintained in the open-label 12-week extension study. Results from pharmacometric modeling of the full clinical data (i.e., from baseline of the double-blind study to the end of the open label extension study) indicates that the data are best characterized by a combined symptomatic and disease modifying drug effect model. Meaning that ANAVEX®2-73 (blarcamesine) exhibited both symptomatic and disease modifying effects in the treatment of Rett syndrome in a clinical setting.

Patients assigned first to ANAVEX®2-73 (blarcamesine) in the double-blind part of the study and who continued on ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) study had a statistically significant (p = 0.01147) reduction in disease severity when compared with patients assigned first to placebo in the double-blind part of the study and who then received ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) part of the study – a criterion for classification as a disease-modifying agent.

Continued improvement from the drug, as measured with the Rett Syndrome Behavior Questionnaire (RSBQ) total score, was observed from the start of the double-blind study to the end of the open-label extension part for patients continuing on ANAVEX®2-73 (blarcamesine). Patients previously on placebo, who switched to ANAVEX®2-73 (blarcamesine) in the OLE part of the study experienced improvement during the OLE part.

Additionally, disease progression, which is defined as the change in Rett syndrome disease severity with time, was also reduced with long-term treatment with ANAVEX®2-73 (blarcamesine).
Patients assigned first to ANAVEX®2-73 (blarcamesine) in the double-blind part of the study and who continued on ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) study had a statistically significant (p = 0.01752) reduction in disease progression when compared with patients assigned first to placebo in the double-blind part of the study and who then received ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) part of the study – a criterion for classifying a drug as a disease-modifying agent.

Patients assigned to ANAVEX®2-73 (blarcamesine) at the start of the double-blind study experienced more benefits of drug effect than could be explained by symptomatic benefit alone – hence, ANAVEX®2-73 (blarcamesine) exhibited both symptomatic and disease-modifying effect.

The reduction in the annual rate of disease progression for those patients, who continued on ANAVEX®2-73 (blarcamesine) was over 3-fold greater, relative to those who switched from placebo to ANAVEX®2-73 (blarcamesine): Ratio of reduction in the annual rate of disease progression = 3.17 (Reduced disease progression rate [Double-blind Part/ OLE — ANAVEX®2-73/ ANAVEX®2-73] = -1.383/year; Reduced disease progression rate [Double-blind Part/ OLE — Placebo/ ANAVEX®2-73] = -0.4357/year).

Anavex plans to submit the data for publication in a peer-reviewed medical journal.