Anavex 2-73 Shows Improvement in Pediatric Rett Syndrome But Misses Key Endpoint

Children with Rett syndrome who received Anavex 2-73 (blarcamesine) showed improvement on the Rett Syndrome Behaviour Questionnaire (RSBQ) but failed to meet a trial key endpoint for Clinical Global Impression – Improvement (CGI-I), according to biopharmaceutical developer Anavex Life Sciences Corp.

The double-blind phase 2/3 trial included 92 pediatric patients, ages 5 through 17 years, with Rett syndrome. Among them, 62 patients were randomized to 30 mg of Anavex 2-73 and 30 patients to placebo for 12 weeks.

After 12 weeks, scores on the 45-question RSBQ, a co-primary endpoint, improved in children who received Anavex 2-73. The other co-primary endpoint, the CGI-I, was not met, Anavex reported.

Patients who received Anavex 2-73 improved a least squares mean of 12.93 points in RSBQ total score compared with 8.32 points in patients who received placebo. The 4.61-point difference was not statistically significant.

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Anavex 2-73 demonstrated a rapid onset of action. After 4 weeks of treatment, RSBQ total scores improved an average 10.32 points with Anavex 2-73 compared with 5.67 with placebo.

The 4.65-point difference between the patient groups was statistically significant.

A key secondary endpoint, the Anxiety, Depression, and Mood Scale (ADAMS), trended in favor of Anavex 2-73. Scores on all RSBQ and ADAMS subscales improved over the course of the study, Anavex reported.

The trial showed a large placebo effect, which Anavex suggested may have masked the therapeutic effect of Anavex 2-73.

“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,” said Anavex chief scientific officer Walter E. Kaufmann, MD. “We intend to further assess the collective results and discuss with the regulatory authorities next steps.”

The trial revealed no new safety signals. More than 90% of participants chose to continue into a 48-week open-label extension study, which is ongoing, the company reported.

Reference

Anavex Life Sciences provides an update on Rett syndrome program. News release. Anavex Life Sciences Corp.; January 2, 2024. Accessed January 26, 2024.