US Phase 2 Trial of Anavex 2-73 Surpasses Initial Enrollment Goal

U.S. enrollment for a Phase 2 clinical trial of investigational therapy Anavex 2-73 (blarcamesine) for Rett syndrome has surpassed its initial target number of participants by nearly 50%.

Anavex Life Sciences announced in a press release that it expects to report top-line results later this year. The study, known as ANAVEX2-73-RS-001 (NCT03758924), is still enrolling women ages 18–45 in the U.S. More information about locations and contacts is available here.

“We are excited to complete enrollment in this carefully conducted, multicenter study with ANAVEX 2-73 (blarcamesine) in Rett syndrome and look forward to reporting the results later this year,” Christopher U. Missling, PhD, president and CEO of Anavex, said in a press release. 

Anavex 2-73  is a small-molecule given orally to activate the Sigma-1 receptor (S1R) protein and ensures correct protein folding. By reducing the buildup of toxic misfolded proteins in nerve cells, Anavex 2-73 is thought to reduce brain inflammation, oxidative stress, and mitochondrial impairment. (Oxidative stress results from excessive levels of free radicals, and mitochondria are the energy-producing structures in cells.)

The double-blind trial is measuring the safety, tolerability and efficacy of Anavex 2-73 in 21 adults with Rett syndrome. The study now has exceeded that recruitment goal by almost 50%. Participants are assigned randomly to receive either Anavex 2-73 or a placebo daily for seven weeks.

Due to the COVID-19 pandemic, screening, enrollment and other trial activities were done through at-home visits.

The trial’s efficacy endpoints, or goals, include improvements in the caregiver-reported Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression Improvement Scale.

Early data from six patients showed that Anavex 2-73 led to improvements in both tools. Benefits also were seen in the RSBQ Hand Behaviours and Breathing Abnormalities component scores.

The findings also revealed an association between both measures of Rett severity and glutamate levels, a key biomarker of disease development that drives the activation of nerve cells.

After completing the trial, participants may join an open-label extension study that will further evaluate the therapy for 12 weeks.

A Phase 2 study with a similar design, called AVATAR (NCT03941444), is currently recruiting 30 women with Rett syndrome in Australia. More information and locations is available here.

Another study, a Phase 2/3 trial named EXCELLENCE (NCT04304482), is evaluating the safety, tolerability and efficacy of Anavex 2-73 compared to a placebo in girls with Rett syndrome, ages 5–18 years. The study also is taking place in Australia, more information here.

In a mouse model of Rett syndrome, Anavex 2-73 improved motor skills, acoustic responses, and visual acuity. The therapy also lessened abnormal movements and ease breathing in the mice.

Anavex 2-73 has been granted fast track, orphan drug and rare pediatric disease designations for the treatment of Rett syndrome by the U.S. Food and Drug Administration.