Anavex Life Sciences Announces Completion of Phase 2/3 Rett Syndrome Clinical Trial


Anavex Life Sciences Corp. recently announced the completion of dosing of all participants of the placebo-controlled EXCELLENCE Phase 2/3 study ANAVEX2-73-RS-003 in pediatric patients with Rett syndrome. The company expects to announce topline results from this study in the second half of this year.

ANAVEX2-73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1) which, data suggest, is pivotal to restoring cellular homeostasis and promoting neuroplasticity.

The completion of the randomized, placebo-controlled EXCELLENCE Phase 2/3 study ANAVEX2-73-RS-003 for the treatment of 92 pediatric patients with Rett syndrome ages ≥ 5 years to 17 (inclusive) was preceded by the successful completion of both placebo-controlled Phase 2 US (ANAVEX2-73-RS-001), and Phase 3 AVATAR (ANAVEX2-73-RS-002) studies in adult patients with Rett syndrome.

The multi-center, double-blind clinical EXCELLENCE study (ANAVEX2-73-RS-003) in pediatric patients is measuring safety, tolerability, and efficacy of daily oral ANAVEX2-73 (blarcamesine) doses or placebo. After completing the double-blind study, eligible participants are able to join a voluntary open-label extension study of ANAVEX2-73 (blarcamesine).

In communication with the FDA, the company received the agency’s input on the study endpoints, which were utilized in this clinical study. The Rett Syndrome Behavior Questionnaire (RBSQ) total score and Clinical Global Impression Improvement Scale (CGI-I) score are co-primary endpoints in the statistical analysis plan with specified linear mixed-effects models for repeated measures (MMRM) as the primary analysis methods.

ANAVEX2-73 (blarcamesine) had previously received Fast Track designation, Rare Pediatric Disease designation and Orphan Drug designation from the FDA for the treatment of Rett syndrome.

“We would like to thank the investigators and clinical site coordinators as well as all the participating families for their dedication to this clinical study completed with ANAVEX2-73 (blarcamesine),” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “Rett syndrome is a devastating, 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, hence we continue our fast-paced development program of ANAVEX2-73 (blarcamesine) in Rett syndrome.”

Rett syndrome is a rare, non-inherited genetic postnatal progressive neurodevelopmental disorder that occurs almost exclusively in girls and leads to severe impairments, affecting nearly every aspect of the child’s life: their ability to speak, walk, eat and even breathe easily. The hallmark of Rett syndrome is near constant repetitive hand movements while awake. It 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, slowed brain and head growth, problems with walking, seizures and intellectual disability. There is currently no cure for Rett syndrome and treatment of the disorder is symptomatic. Management of symptoms is done through a multidisciplinary approach utilizing medication for motor difficulties, breathing irregularities and control of seizures through anticonvulsant drugs. Rett syndrome is caused by mutations in the MECP2 gene and strikes all racial and ethnic groups and occurs worldwide in approximately one in every 10,000 to 15,000 live female births.

Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex’s lead drug candidate, ANAVEX2-73 (blarcamesine), has successfully completed a Phase 2a and recently a Phase 2b/3 clinical trial for Alzheimer’s disease, a Phase 2 proof-of-concept study in Parkinson’s disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. ANAVEX2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson’s Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX2-73 for the treatment of Parkinson’s disease. ANAVEX3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. For more information, visit www.anavex.com.