NEW YORK – Anavex Life Sciences Corp. (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated 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, today announced that the Independent Data Safety Monitoring Board (DSMB) for the Company’s ongoing clinical trial program, including the late stage AVATAR (ANAVEX®2-73-RS-002) [1], EXCELLENCE (ANAVEX®2-73-RS-003) [2] and the U.S. Rett syndrome extension study (ANAVEX®2-73-RS-EP-001) of its investigational compound ANAVEX®2-73 (blarcamesine) has completed its recent pre-planned review of the respective interim safety data for these three separate clinical studies.
Upon review of the interim safety data, the DSMB made the following recommendation for the randomized, double-blind, placebo-controlled AVATAR (ANAVEX®2-73-RS-002) study in adult patients with Rett syndrome:
• The DSMB recommendation is to continue the studies without modification.
Upon review of the interim safety data, the DSMB made the following recommendation for the randomized, double-blind, placebo-controlled EXCELLENCE (ANAVEX®2-73-RS-003) study in pediatric patients with Rett syndrome:
• The DSMB recommendation is to continue the studies without modification.
Upon review of the interim safety data, the DSMB made the following recommendation for the open-label extension U.S. Rett syndrome (ANAVEX®2-73-RS-EP-001) study in adult patients with Rett syndrome:
• The DSMB recommendation is to continue the studies without modification.
DSMBs are committees commonly used in clinical trials to protect the interests of the patients and the integrity of the study data in ongoing trials.
Based on the previously reported results of the first placebo-controlled U.S. Phase 2 (ANAVEX®2-73-RS-001) [3] study in adult patients with Rett syndrome, Anavex is planning to meet with the 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.
The respective ongoing placebo-controlled Phase 2 and Phase 2/3 ANAVEX®2-73 clinical studies in adult (AVATAR) and pediatric (EXCELLENCE) patients with Rett syndrome are expected to be completed by mid 2021 and 2H 2021, respectively.
ANAVEX®2-73 activates the sigma-1 receptor (SIGMAR1). Data suggests that activation of SIGMAR1 results in the restoration of complete housekeeping function within the body and is pivotal to restoring neural cell homeostasis and promoting neuroplasticity. [4]
PET scan data previously confirmed dose-dependent target engagement of SIGMAR1 with ANAVEX®2-73. [5]
Anavex Life Sciences’ product portfolio includes small drug molecule lead candidate ANAVEX®2-73 for the treatment of Alzheimer’s disease, Parkinson’s disease and Rett syndrome.
About ANAVEX®2-73-RS-002 AVATAR Clinical Study (NCT03941444)
The Phase 2 trial is 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 33 adult patients with Rett syndrome over a 7-weeks treatment period incorporating precision medicine biomarkers. Preceding the placebo-controlled randomization of 30 patients (Part B), a 3-patient cohort (Part A) underwent a pharmacokinetic (PK) 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 additional 48 weeks within the open label extension protocol.
About ANAVEX®2-73-RS-003 EXCELLENCE Clinical Study (NCT04304482)
The Phase 2/3 trial is a randomized double-blind, placebo-controlled safety, tolerability, pharmacokinetic and efficacy study of oral liquid ANAVEX®2-73 to treat Rett syndrome in at least 69 pediatric patients with Rett syndrome over a 12-weeks treatment period incorporating precision medicine biomarkers. All patients who completed the study are eligible to continue to receive ANAVEX®2-73 for additional 48 weeks within the open label extension protocol.
About ANAVEX®2-73-RS-001 U.S. Clinical Study (NCT03758924)
The Phase 2 trial is 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 31 adult patients with Rett syndrome over a 7-weeks treatment period were evaluated incorporating precision medicine biomarkers. Preceding the placebo-controlled randomization of 25 patients (Part B), a 6-patient cohort (Part A) underwent a 7-weeks pharmacokinetic (PK) assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX®2-73. All patients who completed in the study were eligible to continue to receive ANAVEX®2-73 under a 36-week open label extension protocol (ANAVEX®2-73-RS-EP-001).
About Rett Syndrome
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: their ability to speak, walk, eat and easily breathe. 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.
Rett syndrome is caused by mutations in the MECP2 gene and strikes all racial and ethnic groups. The disease occurs worldwide in approximately one in every 10,000 to 15,000 live births. The population of patients with Rett syndrome is estimated to be approximately 11,000 patients in the U.S. There is currently no cure for Rett syndrome.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of differentiated 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, ANAVEX®2-73 (blarcamesine), completed successfully a Phase 2a clinical trials for Alzheimer’s disease and a Phase 2 proof-of-concept study in Parkinson’s disease dementia and a Phase 2 study in adult patients with Rett syndrome. ANAVEX®2-73 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. ANAVEX®2-73 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 ANAVEX®2-73 for the treatment of Parkinson’s disease. ANAVEX®3-71, which targets sigma-1 and 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, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the company on Twitter, Facebookand LinkedIn.
Contact:
Anavex Life Sciences Corp.
Research & Business Development
Toll-free: 1-844-689-3939
[email protected]
Investors:
Andrew J. Barwicki
Investor Relations
516-662-9461
[email protected]
References:
[1] ClinicalTrials.gov Identifier: NCT03941444
[2] ClinicalTrials.gov Identifier: NCT04304482
[3] ClinicalTrials.gov Identifier: NCT03758924
[4] Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets.
[5] https://assets.researchsquare.com/files/rs-189177/v1/65385792-095a-4505-90c4-c0b85c76dbd1.pdf.