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Replies to post #316071 on Anavex Life Sciences Corp (AVXL)
06/21/21 7:03 AM
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06/21/21 7:16 AM
Anavex Life Sciences Announces ANAVEX®2-73 (Blarcamesine) Biomarker Correlated with Efficacy Endpoints in Placebo-Controlled U.S. Phase 2 Clinical Trial for the Treatment of Adult Patients with Rett Syndrome
ANAVEX®2-73 treatment resulted in significant increase in the expression of the SIGMAR1 mRNA biomarker that significantly correlated with improvements in the two primary clinical efficacy endpoints RSBQ (p = 0.035) and CGI-I (p = 0.029)
Data strengthens milestone to advance regulatory approval pathway for adult patients with Rett syndrome and continued development in other autism spectrum disorders
NEW YORK – June 21, 2021 – 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) disorders, today reported predictive biomarker of response established with SIGMAR1 mRNA expression correlates significantly with responses in primary clinical efficacy endpoints from the U.S. Phase 2 randomized, double-blind, placebo-controlled trial of ANAVEX®2-73 (blarcamesine) in adult female patients with Rett syndrome.
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. [1] Recent independent findings strengthen the understanding of the beneficial effect of SIGMAR1 activation as compensatory mechanism to chronic CNS diseases. [2]
Rett syndrome is a chronic CNS disease caused by a spontaneous mutation of one gene, MECP2. This study demonstrates for the first-time that a biomarker correlates with clinical efficacy in Rett syndrome. ANAVEX®2-73 treatment resulted in increases in the mRNA expression of SIGMAR1, the gene coding for the receptor targeted by ANAVEX®2-73, which correlated with clinical efficacy as measured by both primary efficacy endpoints (ITT population), namely RSBQ (p = 0.035) and CGI-I (p = 0.029).
In addition, prespecified patients with WT SIGMAR1 in the clinical trial demonstrated a clinically meaningful and statistically significant 14.5-point (p = 0.009) improvement over placebo in the RSBQ total score, the trial’s key efficacy endpoint. This magnitude of the improvement with ANAVEX®2-73 compares favorably to published data currently in clinical development, which reported an average difference of 4.4 points in RSBQ total score versus placebo, despite an advantage of higher dose and lower age compared to ANAVEX®2-73-RS-001 trial. [3]
The RSBQ demonstrated balanced improvements across all the instrument’s subscales during the trial period of 7 weeks, including general mood, breathing, hand behavior, repetitive face movements, body rocking, night-time behavior, fear/anxiety, walking/standing.
The Anxiety, Depression, and Mood Scale (ADAMS), which is a measure of anxiety and mood symptoms in individuals with intellectual disability,[4] has been clinically validated for use in Rett syndrome[5] and in Fragile X syndrome,[6] demonstrated clinically meaningful and statistically significant 12.9-point (p = 0.005) improvement for ANAVEX®2-73 treated adult patients with Rett syndrome vs placebo in prespecified patients with WT SIGMAR1.
The ADAMS also demonstrated balanced improvements across all different subscales during the trial period of 7 weeks, including manic/hyperactive behavior, depressed mood, social avoidance, general anxiety, obsessive compulsive behavior.
“The biomarker-driven clinical evidence is very exciting and opens the possibility of successful treatment for both adults and children with Rett syndrome and early interventions for modifying the course of the disease,” commented Walter E. Kaufmann, MD, Principal Investigator and Chief Medical Officer of Anavex. “The outcome of this trial is very promising in terms of both safety and clinical improvement. Despite the challenges of the older age of the cohort (patients were on average 24 years of age) and the relatively low dose (5 mg daily), ANAVEX®2-73 demonstrated clinically meaningful improvements in outcome measures evaluating multiple impairments, which are supported by correlations with objective biomarkers.”
With this convincing biomarker correlating efficacy data of U.S. Phase 2 (ANAVEX®2-73-RS-001)[7] 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 study was supported by the Rettsyndrome.org Foundation.
ANAVEX®2-73 is currently being evaluated for Rett syndrome in two other ongoing late-stage placebo-controlled clinical studies: The AVATAR trial in adult Rett syndrome (ANAVEX®2-73-RS-002)[8] and the EXCELLENCE pediatric Rett syndrome trial (ANAVEX®2-73-RS-003)[9].
“These are strong and consistent data demonstrating biomarker-correlated rapid and clinically meaningful improvements in key measures of Rett syndrome symptoms in the ANAVEX®2-73 treatment group compared to placebo,” said Christopher U. Missling, PhD, President & Chief Executive Officer of Anavex. “Our team is dedicated to provide for this urgent unmet need of patients with Rett syndrome, and we believe our ANAVEX®2-73 Rett syndrome program sets us on a course to potentially offer a new, unique and mechanistically differentiated treatment option also for other diseases associated with autism spectrum disorder.”
Anavex Life Sciences’ product portfolio platform includes small molecule drug lead candidate ANAVEX®2-73 for the treatment of Alzheimer’s disease, Parkinson’s disease and Rett syndrome and ANAVEX®3-71 for frontotemporal dementia.
06/21/21 7:50 AM
