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Anavex Life Sciences Provides an Update on Rett Syndrome Program

Anavex Announces Topline Results from Phase 2/3 EXCELLENCE Clinical Study in Pediatric Rett Syndrome Validation from Real World Evidence (RWE) of Rett Syndrome Patients under Compassionate Use Authorization

NEW YORK – January 2, 2024

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 today reported topline results from the randomized, double-blind, placebo-controlled, Phase 2/3 EXCELLENCE clinical trial, which evaluated the clinical efficacy, safety, and tolerability of 30 mg ANAVEX®2-73 in 92 pediatric patients with Rett syndrome (RTT) between the ages of 5 through 17 years. Participants were randomized 2:1 (ANAVEX®2-73 [62 patients] to placebo [30 patients]) for 12 weeks, followed by a week 16 safety visit. As well, Anavex reported positive Real World Evidence (RWE) feedback from Rett syndrome patients under Compassionate Use Authorization.


This was the very first study of ANAVEX®2-73 in pediatric patients with Rett syndrome. After 12 weeks, the study showed improvement on the key co-primary endpoint Rett Syndrome Behaviour Questionnaire (RSBQ), which is a detailed 45-item questionnaire for assessing multiple Rett syndrome characteristics by the patients’ caregivers. The other co-primary endpoint, the Clinical Global Impression – Improvement scale (CGI-I), which represents a less granular assessment by the site investigators using a seven-point scoring (one=“very much improved” to seven=“very much worse”), was not met.


In an ad-hoc analysis, using the predefined mixed-effect model for repeated measure (MMRM) method, after 12 weeks of treatment, ANAVEX®2-73-treated patients improved LS Mean (SE) -12.93 (2.150) points on their RSBQ total score compared to LS Mean (SE) -8.32 (2.537) points in placebo-treated patients. The LS Mean difference (SE) of -4.61 (2.439) points between treated and placebo groups did not reach statistical significance (n=77; p=0.063). ANAVEX®2-73-treated patients demonstrated a rapid onset of action with improvements at 4 weeks after treatment with a RSBQ total score LS Mean (SE) -10.32 (2.086) points in the drug-treated group compared to a LS Mean (SE) -5.67 (2.413) points in placebo-treated patients. The LS Mean difference of -4.65 (2.233) points between treated and placebo groups was statistically significant (n=77; p=0.041).


When looking at other placebo-controlled Rett syndrome trials, ANAVEX®2-73 compares favorably in terms of absolute RSBQ improvements, with the caveat that cross trials comparisons have their limitations.


The key secondary endpoint, the Anxiety, Depression, and Mood Scale (ADAMS), trended favorably. In the same analysis, scores for all RSBQ and ADAMS subscales improved over the course of the study. Collectively, the RSBQ and ADAMS demonstrated improvements in multiple areas, impacting positively in particular repetitive movements, nighttime disruptive behaviors and social avoidance.


In the EXCELLENCE study, a large placebo effect was observed which may have masked the compound’s therapeutic effect. Anavex believes to have identified the probable causes.


Walter E Kaufmann, MD, Chief Scientific Officer of Anavex commented, “We believe that a high placebo response may have masked the therapeutic effect of this innovative orally available molecule. High placebo responses are well documented especially in pediatric clinical studies. Although data analysis is ongoing, the early conclusion is that the placebo rate could have been higher in the study due to a slight imbalance in disease severity at baseline, across the treatment arms, and the 2 to 1 drug to placebo randomization ratio. We intend to further assess the collective results and discuss with the regulatory authorities next steps.”


A preliminary review of the safety results indicates there were no new safety signals in the EXCELLENCE study, reinforcing the favorable and manageable safety profile observed with ANAVEX®2-73 to date. The most common treatment-related adverse events in the drug-treated group were somnolence and lethargy and were predominantly mild to moderate in severity. There were no clinically meaningful changes observed in SAEs associated with known risks of ANAVEX®2-73.


Over 91% of patients completing the trial continued into a 48-week open-label extension study (OLE), which is ongoing. Upon patient’s caregivers and investigators request, Anavex has established Compassionate Use Programs in Canada, Australia, and the UK for pediatric patients upon completion of the OLE study, similarly to its existing program for adult patients with Rett syndrome. To date, of the pediatric patients who completed the OLE, 93% have joined the Compassionate Use Program. This rate is comparable to the Compassionate Use level seen for adult patients which is over 96%. As of today, some patients with Rett syndrome have been on ANAVEX®2-73-treatment for over 4 years, combined OLE and Compassionate Use Program.


The high enrollment rates in the OLE and the high level of requests for the Compassionate Use Program provide solid numerical evidence for the reported positive Real World Evidence (RWE) from patients with Rett syndrome under Compassionate Use Authorization. Families whose children were previously on drug or placebo in the placebo-controlled trial commented favorably on the improvement of their child’s daily life due to ANAVEX®2-73 treatment in the Compassionate Use Program. E.g.:




See related link for more video comments from parents at RSAA/parent stories.


“We believe that ANAVEX®2-73, as a new, potential convenient treatment option in the future, can contribute to patients and healthcare professionals by addressing unmet needs in the treatment of Rett syndrome,” stated Christopher U Missling, PhD, President and Chief Executive Officer. “Based on these study results, we will continue to be committed to the Rett syndrome and rare disease community, given also the prior successful two placebo-controlled studies in adult patients with Rett syndrome. We express our deep gratitude for the commitment of the study participants and their caregivers, whose dedication and generous participation in clinical trials made this research possible.”


The EXCELLENCE Phase 2/3 study ANAVEX®2-73-RS-003 was preceded by the successful completion of both placebo-controlled Phase 2 U.S. (ANAVEX®2-73-RS-001) [1], and Phase 3 AVATAR (ANAVEX®2-73-RS-002) [2] studies in adult patients with Rett syndrome.


ANAVEX®2-73 had previously received Fast Track designation, Rare Pediatric Disease designation and Orphan Drug designation from the FDA for the treatment of Rett syndrome.


In addition to Rett syndrome, Anavex is evaluating ANAVEX®2-73 in other neurodevelopmental disorders, including Fragile X syndrome, and in neurodegenerative disorders like Parkinson’s disease. Anavex recently received agreement from the Committee for Medicinal Products for Human Use (CHMP) within the European Medicines Agency (EMA) for the submission of a Marketing Authorisation Application of oral blarcamesine for Alzheimer’s disease. 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 development (6 to 18 months) followed by slowing of development, loss of purposeful use of the hands and spoken language, distinctive hand movements, problems with walking, seizures and intellectual disability. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease. 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, striking all racial and ethnic groups and occurring 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 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 You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.

Forward-Looking Statements

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.

For Further Information: Anavex Life Sciences Corp.

Research & Business Development

Toll-free: 1-844-689-3939

Email: Investors:

Andrew J. Barwicki

Investor Relations

Tel: 516-662-9461

Email: [1] Identifier: NCT03758924

[2] Identifier: NCT03941444



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