NEW YORK – June 28, 2023
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (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 long-term clinical study results from the U.S. ANAVEX®2-73-RS-001 (NCT03758924) study demonstrate disease-modifying effect of ANAVEX®2-73 (blarcamesine) for adult patients with Rett syndrome.
Usually, symptomatic therapies treat the symptoms of the disease but do not address the underlying cause of the disease. Disease-modifying therapies target the underlying cause of the disease.
ANAVEX®2-73 (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. 
In the U.S. ANAVEX®2-73-RS-001 trial, of all 25 patients who both started and completed the randomized, double-blind, placebo-controlled study, 24 patients voluntarily enrolled in the 12-week open-label extension (OLE) study, receiving once-daily oral liquid ANAVEX®2-73 (blarcamesine) formulation for further evaluation of long-term safety, tolerability, and effectiveness of ANAVEX®2-73 (blarcamesine) in patients with Rett syndrome. The 12-week extension study was subsequently further extended to 36 weeks.
The effect of ANAVEX®2-73 (blarcamesine) in the double-blind part of the U.S. ANAVEX®2-73-RS-001 study was maintained in the open-label 12-week extension study. Results from pharmacometric modeling of the full clinical data (i.e., from baseline of the double-blind study to the end of the open label extension study) indicates that the data are best characterized by a combined symptomatic and disease modifying drug effect model. Meaning that ANAVEX®2-73 (blarcamesine) exhibited both symptomatic and disease modifying effects in the treatment of Rett syndrome in a clinical setting.
Patients assigned first to ANAVEX®2-73 (blarcamesine) in the double-blind part of the study and who continued on ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) study had a statistically significant (p = 0.01147) reduction in disease severity when compared with patients assigned first to placebo in the double-blind part of the study and who then received ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) part of the study – a criterion for classification as a disease-modifying agent.
Continued improvement from the drug, as measured with the Rett Syndrome Behavior Questionnaire (RSBQ) total score, was observed from the start of the double-blind study to the end of the open-label extension part for patients continuing on ANAVEX®2-73 (blarcamesine). Patients previously on placebo, who switched to ANAVEX®2-73 (blarcamesine) in the OLE part of the study experienced improvement during the OLE part.
Additionally, disease progression, which is defined as the change in Rett syndrome disease severity with time, was also reduced with long-term treatment with ANAVEX®2-73 (blarcamesine).
Patients assigned first to ANAVEX®2-73 (blarcamesine) in the double-blind part of the study and who continued on ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) study had a statistically significant (p = 0.01752) reduction in disease progression when compared with patients assigned first to placebo in the double-blind part of the study and who then received ANAVEX®2-73 (blarcamesine) during the open-label extension (OLE) part of the study – a criterion for classifying a drug as a disease-modifying agent.
Patients assigned to ANAVEX®2-73 (blarcamesine) at the start of the double-blind study experienced more benefits of drug effect than could be explained by symptomatic benefit alone – hence, ANAVEX®2-73 (blarcamesine) exhibited both symptomatic and disease-modifying effect.
The reduction in the annual rate of disease progression for those patients, who continued on ANAVEX®2-73 (blarcamesine) was over 3-fold greater, relative to those who switched from placebo to ANAVEX®2-73 (blarcamesine): Ratio of reduction in the annual rate of disease progression = 3.17 (Reduced disease progression rate [Double-blind Part/ OLE — ANAVEX®2-73/ ANAVEX®2-73] = -1.383/year; Reduced disease progression rate [Double-blind Part/ OLE — Placebo/ ANAVEX®2-73] = -0.4357/year).
Anavex plans to submit the data for publication in a peer-reviewed medical journal.
ANAVEX®2-73 (blarcamesine) has previously received Fast Track designation, Rare Pediatric Disease designation and Orphan Drug designation from the FDA for the treatment of Rett syndrome.
“We believe these promising long-term clinical results in adult patients with Rett syndrome provides further support of the beneficial effect of ANAVEX®2-73 (blarcamesine) for patients with Rett syndrome,” 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. We are looking forward to the upcoming read-out of the ANAVEX®2-73 (blarcamesine) EXCELLENCE Phase 2/3 Rett syndrome clinical trial in pediatric patients with Rett syndrome.”
About 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.
About Anavex Life Sciences Corp.
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, ANAVEX®2-73 (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. 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 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, 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, Facebook, Instagram and LinkedIn.
Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.
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Email: email@example.com Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets. Rett Syndrome Behavior Questionnaire (RSBQ) total score is key primary endpoint in the completed multi-center, double-blind clinical EXCELLENCE Phase 2/3 study ANAVEX®2-73-RS-003 (NCT04304482) in pediatric patients with Rett syndrome. Topline results from this study are expected in the second half of this year.