Anavex Life Sciences Initiates Placebo-Controlled U.S. Phase 2 Clinical Trial of ANAVEX®3-71 in Schizophrenia

Rhea-AI Summary

Anavex Life Sciences Corp. announces the screening of the first patient in the Phase 2 clinical study of ANAVEX®3-71 for schizophrenia treatment. The trial aims to investigate positive, negative, and cognitive symptoms of schizophrenia using a novel mechanism of action.

Insights

Medical Research Analyst

The screening of the first patient for Anavex's Phase 2 clinical trial of ANAVEX®3-71 ahead of schedule is a notable development in the field of schizophrenia treatment. The drug's unique mechanism, targeting both SIGMAR1 and M1 muscarinic receptors, could represent a significant advancement in addressing the multifaceted symptoms of schizophrenia. Current antipsychotics often fall short in treating negative and cognitive symptoms, which are important for patient quality of life. If ANAVEX®3-71 can demonstrate efficacy without the common side effects of existing treatments, it could disrupt the market and provide a new standard of care for patients.

Furthermore, Anavex's use of advanced biomarkers for assessing drug efficacy, such as EEG/ERP, could enhance the precision of clinical outcomes. This precision medicine approach aligns with current trends in drug development, potentially increasing the likelihood of successful treatment outcomes and regulatory approval. However, the drug is still in the early stages of clinical testing and its safety and efficacy must be rigorously evaluated in a larger patient population before any conclusions can be drawn.

Financial Analyst

From a financial perspective, the advancement of ANAVEX®3-71 into Phase 2 trials ahead of schedule could be viewed positively by investors and market analysts. The proactive approach of Anavex Life Sciences Corp. in addressing a significant unmet medical need presents potential growth opportunities for the company. The schizophrenia treatment market is substantial, with a global prevalence of nearly 24 million people. A successful entry could lead to a considerable increase in market share and revenue for Anavex.

However, investors should consider the inherent risks associated with clinical-stage biopharmaceutical investments. The path from Phase 2 trials to market approval is fraught with potential setbacks, including trial failures, regulatory hurdles and competition from other pharmaceutical companies. The long-term financial impact will depend on the trial outcomes, the drug's efficacy and safety profile and the ability to secure regulatory approval and market access. In the short term, positive trial results could lead to stock price volatility as investors react to each development.

Market Research Analyst

The schizophrenia drug market is characterized by a high demand for treatments that can address the full spectrum of symptoms with fewer side effects. ANAVEX®3-71's dual mechanism of action could potentially meet this demand, which may lead to a significant shift in treatment paradigms if the drug is approved. Moreover, the integration of biomarker technology for patient selection and outcome assessment reflects a growing trend in personalized medicine, which is becoming increasingly important in differentiating products in the pharmaceutical market.

The success of ANAVEX®3-71 will also depend on the competitive landscape, including the entry of generics and other novel therapies. Market adoption will hinge not only on clinical efficacy but also on factors such as pricing, reimbursement and the ability to educate healthcare providers about the benefits of the new treatment approach. Anavex's strategic partnerships, such as those contributing to EEG/ERP biomarker development, could play a pivotal role in navigating these market dynamics.

First patient screened ahead of schedule

Trial to investigate positive, negative, and cognitive domains of schizophrenia

ANAVEX^®3-71’s differentiated dual novel mechanism of action offers the potential to synergistically activate both SIGMAR1 and M1 muscarinic receptors and treat all symptom domains of schizophrenia without the side effects of standard of care antipsychotics

NEW YORK, March 18, 2024 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today announced that the first patient in its U.S. FDA cleared placebo-controlled Phase 2 clinical study of ANAVEX^®3-71 for the treatment of schizophrenia has been screened ahead of schedule.

“Initiating our Phase 2 trial of ANAVEX^®3-71 in schizophrenia ahead of schedule is a testament to the hard work and dedication of our clinical study team,” stated Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “Schizophrenia is a challenging disorder that can impair social and occupational functions and overall quality of life for the nearly 24 million people affected worldwide. Following on from our positive initial Phase 1 results in healthy volunteers, our Phase 2 study will apply novel neuroinflammatory, metabolomic, and transcriptomic biomarkers at the intersection of schizophrenia pathophysiology and ANAVEX^®3-71’s novel, dual mechanism of action, with the goal of addressing the large unmet need in this patient population. We are excited to build on our diverse Precision Medicine Platform, which advanced blarcamesine (ANAVEX^®2-73) onto a regulatory pathway for potential treatment of Alzheimer’s disease.”

ANAVEX^®3-71’s differentiated mechanism is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects.^1,2 This novel mechanism of action offers the potential to treat all symptom domains of schizophrenia -- positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making) -- without the side effects of standard of care antipsychotics, which do not adequately address all symptom domains in schizophrenia. ANAVEX^®3-71’s ability to modulate both SIGMAR1 and M1 receptors is expected to potentially address disruptions to neuronal homeostasis observed in individuals with schizophrenia, upstream of the targets leveraged by standard of care medications.

Preceding this study, ANAVEX^®3-71 demonstrated an adequate safety profile in a Phase 1 trial in healthy volunteers.^3,4

ANAVEX^®3-71 Phase 2 Program Outline

The placebo-controlled Phase 2, two-part, in-patient trial, ANAVEX^®3-71-SZ-001 (NCT06245213), will investigate the effects of ANAVEX^®3-71 in patients with schizophrenia.

• Part A is a double-blind, placebo-controlled, multiple ascending dose trial. The results of Part A will be used to select a dose for Part B, a proof-of-concept efficacy, double-blind, placebo-controlled trial.
• Participants will undergo either 10 or 28 days of dosing (Part A and Part B, respectively).
• Standard clinical outcome measures, including the Positive and Negative Syndrome Scale (PANSS), and novel fluid and electrophysiological biomarkers will be assessed.
  

Anavex is leveraging several advances in electroencephalography/event-related potential (EEG/ERP) biomarkers in schizophrenia developed in collaboration with the industry-led ERP Biomarker Qualification Consortium.⁵ This includes a validated, and automated data analysis pipeline for quantitative EEG and ERP biomarkers, as well as normative EEG/ERP data in patients with schizophrenia and matched healthy volunteers. These advances also include recently established relationships between EEG/ERP biomarkers and clinically important measures in schizophrenia.

In addition to the electrophysiological biomarkers, Anavex is applying novel neuroinflammatory, metabolomic, and transcriptomic biomarkers at the intersection of schizophrenia pathophysiology and ANAVEX®3-71’s novel, dual mechanism of action.

About Schizophrenia

Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 34% of people do not respond to therapy, ⁶ with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.⁷

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, schizophrenia 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 and one Phase 2/3 in pediatric patients with Rett syndrome. ANAVEX^®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting SIGMAR1 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 SIGMAR1 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.

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: info@anavex.com

Investors:
Andrew J. Barwicki
Investor Relations
Tel: 516-662-9461
Email: andrew@barwicki.com

¹ Fisher A, Bezprozvanny I, Wu L, et al. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease. Neurodegener Dis. 2016;16(1-2):95-110. doi:10.1159/000440864
² Hall H, Iulita MF, Gubert P, et al. AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease. Alzheimers Dement. 2018;14(6):811-823. doi:10.1016/j.jalz.2017.11.009
³ Fadiran EO, Hammond E, Tran J, et al. Concentration-QTc Relationship from a Single Ascending Dose Study of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for the Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer's Disease. Clin Pharmacol Drug Dev. 2023;12(9):888-901. doi:10.1002/cpdd.1303
⁴ Fadiran EO, Hammond E, Tran J, Missling CU, Ette E. Population-Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease. Clin Pharmacol Drug Dev. 2024;13(1):21-31. doi:10.1002/cpdd.1323
⁵ Cecchi M, Adachi M, Basile A, et al. Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers. Schizophr Res. 2023;254:178-189. doi:10.1016/j.schres.2023.02.018
⁶ Potkin SG, Kane JM, Correll CU, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020;6(1):1. Published 2020 Jan 7. doi:10.1038/s41537-019-0090-z
⁷ Nucifora FC Jr, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019;131:104257. doi:10.1016/j.nbd.2018.08.016

FAQ

What is the ticker symbol of Anavex Life Sciences Corp.?

The ticker symbol of Anavex Life Sciences Corp. is AVXL.

What is the focus of the Phase 2 clinical study of ANAVEX®3-71?

The Phase 2 study aims to investigate the effects of ANAVEX®3-71 in patients with schizophrenia, targeting positive, negative, and cognitive symptoms.

What is the novel mechanism of action of ANAVEX®3-71 for schizophrenia treatment?

ANAVEX®3-71 is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator, offering potential to treat all symptom domains of schizophrenia without standard antipsychotic side effects.

What are the key biomarkers being used in the Phase 2 clinical trial of ANAVEX®3-71?

The trial includes standard clinical outcome measures like PANSS, as well as novel fluid and electrophysiological biomarkers, including EEG/ERP biomarkers and neuroinflammatory, metabolomic, and transcriptomic biomarkers.

What is the significance of screening the first patient ahead of schedule in the Phase 2 clinical study?

Screening the first patient ahead of schedule indicates the efficient progress of the trial and the dedication of the clinical study team towards addressing the unmet need in schizophrenia treatment.