Anavex Life Sciences reported positive top-line results from the phase 3 trial of ANAVEX 2-73 in adult female patients with Rett syndrome as it demonstrated a statistically significant improvement over placebo for the primary efficacy endpoint as well as for all the secondary efficacy endpoints.
The results, though, have met with some skepticism because of changes the company made to the study endpoints earlier this month. In morning trading, Anavex shares fell nearly 14 percent to $11.26 despite what the company is calling a “very large” effect.
Rett syndrome is a non-inherited, genetic, post-natal, progressive neurodevelopmental disorder that occurs almost exclusively in girls and leads to severe impairments, affecting nearly every aspect of the child’s life. The hallmark of Rett syndrome is near constant repetitive hand movements while awake. The disease is characterized by normal early growth and development (6 to 18 months) followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, autistic features, slowed brain and head growth, ataxia, seizures, and intellectual disability. There is currently no cure for Rett syndrome.
ANAVEX 2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors and is in development to treat multiple neurological conditions including Alzheimer’s disease. ANAVEX 2-73 activates the sigma-1 receptor (SIGMAR1). Data suggests that activation of SIGMAR1 results in the restoration of homeostatic function within the body and is pivotal to restoring neural cell balance and the promotion of neuroplasticity. Recent independent findings strengthen the understanding of the beneficial effects of SIGMAR1 activation as a compensatory mechanism to chronic CNS diseases.
The company said in preclinical studies, ANAVEX 2-73 exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy.
The phase 3 trial was a randomized double-blind, placebo-controlled safety, tolerability, pharmacokinetic and efficacy study of oral liquid ANAVEX 2-73 to treat Rett syndrome in a total of 36 adult patients with Rett syndrome over a seven-week treatment period incorporating precision medicine biomarkers. Preceding the placebo-controlled randomization of 33 patients (Part B), a 3-patient cohort (Part A) underwent a pharmacokinetic assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX 2-73. All patients who completed the study are eligible to continue to receive ANAVEX 2-73 for an additional 48 weeks within the open label extension protocol.
In the primary endpoint, a behavioral questionnaire designed for Rett syndrome patients known as RSBQ AUC, ANAVEX 2-73 induced a statistically significant and clinical meaningful improvement in 72.2 percent of patients as compared to 38.5 percent on placebo.
The secondary efficacy endpoints also demonstrated statistically significant and clinical meaningful improvements. For the ADAMS, a measure of emotional behavior symptoms, a significantly higher proportion of ANAVEX 2-73 treated adult patients with Rett syndrome (52.9 percent) than placebo-treated patients (8.3 percent) showed improvement, which corresponded to a Cohen’s d effect size of 0.609 (large). For the CGI-I, more patients achieved clinically meaningful CGI-I response over the treatment duration in the ANAVEX 2-73-treated group (72.2 percent) than in the placebo group (38.5 percent) with a Cohen’s d effect size of 1.91.
Based on the results in this phase 3 study and the prior successful phase 2 (ANAVEX 2-73-RS-001) study in adult patients with Rett syndrome, Anavex is planning to meet with FDA to discuss the approval pathway.
There are 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 for the treatment of Rett syndrome and may be considered for accelerated approval.
“This is now the second successful placebo-controlled study of ANAVEX 2-73 in adult patients with Rett syndrome,” said Christopher Missling, president and CEO of Anavex, “and this phase 3 study builds on the platform potential of ANAVEX 2-73 and its ability to demonstrate clinically meaningful improvements in Rett syndrome symptoms in the ANAVEX 2-73 treatment group compared to placebo.”
Author: Rare Daily Staff
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