ANAVEX RETT STUDY FAILED!!!!!!!!!!!
https://www.anavex.com/post/anavex-life-sciences-provides-update-rett-syndrome-programAnavex Life Sciences Provides an Update on Rett Syndrome ProgramAnavex Announces Topline Results from Phase 2/3 EXCELLENCE Clinical Study in Pediatric Rett SyndromeValidation from Real World Evidence (RWE) of Rett Syndrome Patients under Compassionate Use Authorization
NEW YORK – January 2, 2024Anavex Life Sciences Corp. (“Anavex” or the “Company”
(Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders today reported topline results from the randomized, double-blind, placebo-controlled, Phase 2/3 EXCELLENCE clinical trial, which evaluated the clinical efficacy, safety, and tolerability of 30 mg ANAVEX®2-73 in 92 pediatric patients with Rett syndrome (RTT) between the ages of 5 through 17 years. Participants were randomized 2:1 (ANAVEX®2-73 [62 patients] to placebo [30 patients]) for 12 weeks, followed by a week 16 safety visit. As well, Anavex reported positive Real World Evidence (RWE) feedback from Rett syndrome patients under Compassionate Use Authorization.
This was the very first study of ANAVEX®2-73 in pediatric patients with Rett syndrome. After 12 weeks, the study showed improvement on the key co-primary endpoint Rett Syndrome Behaviour Questionnaire (RSBQ), which is a detailed 45-item questionnaire for assessing multiple Rett syndrome characteristics by the patients’ caregivers. The other co-primary endpoint, the Clinical Global Impression – Improvement scale (CGI-I), which represents a less granular assessment by the site investigators using a seven-point scoring (one=“very much improved” to seven=“very much worse”
, was not met.
In an ad-hoc analysis, using the predefined mixed-effect model for repeated measure (MMRM) method, after 12 weeks of treatment, ANAVEX®2-73-treated patients improved LS Mean (SE) -12.93 (2.150) points on their RSBQ total score compared to LS Mean (SE) -8.32 (2.537) points in placebo-treated patients. The LS Mean difference (SE) of -4.61 (2.439) points between treated and placebo groups did not reach statistical significance (n=77; p=0.063). ANAVEX®2-73-treated patients demonstrated a rapid onset of action with improvements at 4 weeks after treatment with a RSBQ total score LS Mean (SE) -10.32 (2.086) points in the drug-treated group compared to a LS Mean (SE) -5.67 (2.413) points in placebo-treated patients. The LS Mean difference of -4.65 (2.233) points between treated and placebo groups was statistically significant (n=77; p=0.041).
When looking at other placebo-controlled Rett syndrome trials, ANAVEX®2-73 compares favorably in terms of absolute RSBQ improvements, with the caveat that cross trials comparisons have their limitations.
The key secondary endpoint, the Anxiety, Depression, and Mood Scale (ADAMS), trended favorably. In the same analysis, scores for all RSBQ and ADAMS subscales improved over the course of the study. Collectively, the RSBQ and ADAMS demonstrated improvements in multiple areas, impacting positively in particular repetitive movements, nighttime disruptive behaviors and social avoidance.
In the EXCELLENCE study, a large placebo effect was observed which may have masked the compound’s therapeutic effect. Anavex believes to have identified the probable causes.
Walter E Kaufmann, MD, Chief Scientific Officer of Anavex commented, “We believe that a high placebo response may have masked the therapeutic effect of this innovative orally available molecule. High placebo responses are well documented especially in pediatric clinical studies. Although data analysis is ongoing, the early conclusion is that the placebo rate could have been higher in the study due to a slight imbalance in disease severity at baseline, across the treatment arms, and the 2 to 1 drug to placebo randomization ratio. We intend to further assess the collective results and discuss with the regulatory authorities next steps.”
A preliminary review of the safety results indicates there were no new safety signals in the EXCELLENCE study, reinforcing the favorable and manageable safety profile observed with ANAVEX®2-73 to date. The most common treatment-related adverse events in the drug-treated group were somnolence and lethargy and were predominantly mild to moderate in severity. There were no clinically meaningful changes observed in SAEs associated with known risks of ANAVEX®2-73.
Over 91% of patients completing the trial continued into a 48-week open-label extension study (OLE), which is ongoing. Upon patient’s caregivers and investigators request, Anavex has established Compassionate Use Programs in Canada, Australia, and the UK for pediatric patients upon completion of the OLE study, similarly to its existing program for adult patients with Rett syndrome. To date, of the pediatric patients who completed the OLE, 93% have joined the Compassionate Use Program. This rate is comparable to the Compassionate Use level seen for adult patients which is over 96%. As of today, some patients with Rett syndrome have been on ANAVEX®2-73-treatment for over 4 years, combined OLE and Compassionate Use Program.
The high enrollment rates in the OLE and the high level of requests for the Compassionate Use Program provide solid numerical evidence for the reported positive Real World Evidence (RWE) from patients with Rett syndrome under Compassionate Use Authorization. Families whose children were previously on drug or placebo in the placebo-controlled trial commented favorably on the improvement of their child’s daily life due to ANAVEX®2-73 treatment in the Compassionate Use Program. E.g.:
(20min delay)