Board Recommends All Anavex 2-73 Trials Proceed

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by Forest Ray PhD |

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update on Anavex 2-73 trials

An independent monitoring board has recommended that all three ongoing clinical trials of Anavex 2-73 (blarcamesine), an investigational treatment for Rett syndrome, continue without changes, based on a review of interim safety data.

Anavex Life Sciences, the medication’s developer, announced the decision in a press release. Data Safety Monitoring Boards are used in clinical studies to protect the interests of the participants and the integrity of the data.

All three trials — AVATAR (NCT03941444), EXCELLENCE (NCT04304482), and a 36-week extension study of a Phase 2 trial (NCT03758924) — are assessing the safety, tolerability and efficacy of Anavex 2-73.

The EXCELLENCE trial involves children ages 5 to 18 and is expected to conclude in the second half of this year. AVATAR includes women ages 18 to 45 and is expected to conclude by mid-year.

Anavex 2-73 is a small molecule designed to activate the sigma-1 receptor protein, which helps proteins fold into their correct, functional shapes. This is thought to help lower lower cellular stress and aid mitochondria, where cellular energy is produced. Data support benefits in promoting the health and ability of neural cells to adapt, according to Anavex.


Women in the Phase 2 AVATAR study are assigned randomly to receive either Anavex 2-73 or a placebo over seven weeks. After this, they may opt to continue in a 48-week extension study where all receive treatment.

This trial’s main goals are to measure the incidence of adverse events, maximum concentration of Anavex 2-73 in patients’ blood and its variation with time, and how it affects key laboratory findings. Secondary measures include changes in the caregiver-reported Rett Syndrome Behaviour Questionnaire (RSBQ) and in the Clinical Global Impression Improvement Scale (CGI-I) score of disease severity.

The Phase 2/3 EXCELLENCE trial includes a 12-week period with either Anavex 2-73 or placebo, after which children may enroll in an extension study of 48 weeks (almost a year).

This trial primarily seeks to evaluate changes in the RSBQ and CGI-I scores over the course of treatment. Secondary measures include: changes in anxiety, depression, and mood; sleep habits; and seizure frequency.

Based on the results of an earlier Phase 2 trial, Anavex plans to discuss the therapy candidate’s approval pathway with the U.S. Food and Drug Administration (FDA).

Top-line results for that trial (NCT03758924) showed that Anavex 2-73 reduced behavioral problems, disease severity, and glutamate levels without serious side effects among 25 women. (Glutamate, a marker of Rett development, is a chemical messenger that works to activate nerve cells.)

Two-thirds of participants receiving Anavex 2-73 in that study experienced statistically significant improvements in characteristics that can include repetitive hand movements, hyperventilation, and breath holding, compared to 10% on placebo. The investigators began to see clinically meaningful differences between groups as early as four weeks after beginning treatment.

Anavex 2-73 currently holds fast track, rare pediatric disease, and orphan drug designations for the treatment of Rett syndrome from the FDA, all meant to smooth and speed its development process.