Hope Springs Anew in Rett Syndrome as Anavex Trial Confirms Efficacy

New York-based Anavex Life Sciences announced positive topline results from its Phase III AVATAR trial of Anavex 2-73 (blarcamesione) in adult female patients with Rett syndrome. The drug provided a statistically significant improvement compared to placebo for the primary efficacy endpoint in addition to all secondary efficacy endpoints. The drug, which is a daily oral liquid, was well tolerated.

Rett syndrome is a rare neurological disorder that primarily effects girls. It leads to severe speaking, walking, eating and even breathing inabilities. One hallmark is almost constant repetitive hand movements.

The disease is caused by a spontaneous mutation of the MECP2 gene located on the X chromosome. More than 900 different mutations are found on the MECP2 gene, usually in eight different “hot spots.” The severity of Rett syndrome is based on the location, type, severity of the mutation and which X chromosome it occurs in because one X chromosome in females is inactivated. It occurs in about one of every 10,000 female births and is rarer in boys. Those affected can live to middle age or beyond.

Anavex 2-73 activated the sigma-1 receptor (SIGMAR1). It is believed that activating SIGMAR1 restores the homeostatic function within the body, which is needed to restore neural cell balance and promote neuroplasticity.

The study’s primary endpoint was RSBQ AUC (Rett Syndrome Behaviour Questionnaire). The drug resulted in a statistically significant and clinically meaningful improvement in 72.2% of patients compared to 38.5% in the placebo group. Secondary efficacy endpoints included ADAMS, a measure of emotional behavior symptoms.

“The outcomes of this trial have confirmed the promising results of the early lower-dose study in adults with Rett syndrome,” stated Dr. Terence O’Brien, principal investigator of the study. “Anavex 2-73 was not only safe but it also demonstrated clinically meaningful improvements in multiple common areas of impairment, which are known to impair the quality of life of girls and women affected by the disorder.”

Based on the results from this study and a previous Phase II trial, the company plans to meet with the U.S. Food and Drug Administration to discuss an approval pathway. There are currently no FDA-approved drugs for Rett syndrome. Anavex 2-73 has Fast Track designation, Rare Pediatric Disease designation and Orphan Drug designation from the FDA.

“The consistent efficacy across primary and secondary endpoints in the Phase III AVATAR study confirms the potential of Anavex 2-73 for treating Rett syndrome, which has been suggested by a prior Phase II study,” said Dr. Walter E. Kaufmann, chief scientific officer of Anavex. “Moreover, the convergent clinical evidence is supported by parallel changes in blood-based biomarkers of disease, including the key neurotransmitter GABA. This strong body of data opens the possibility of successful treatment for both adults and children with Rett syndrome and early interventions for modifying the course of the disease.”