Anavex Reports Promising Early Biomarker Results from Phase 2 ANAVEX®3-71 Schizophrenia Study

On October 17, 2024, Anavex Life Sciences Corp., a clinical-stage biopharmaceutical company, announced promising initial results from the placebo-controlled Phase 2 clinical study of ANAVEX®3-71 for the treatment of schizophrenia. This study, designated as ANAVEX®3-71-SZ-001, is investigating the effects of ANAVEX®3-71 on specific EEG biomarkers associated with schizophrenia.

The Phase 2 study consists of two parts, with Part A now completed. Part A was a multiple ascending dose study involving 16 participants, who were administered either a placebo, 90 mg of ANAVEX®3-71 daily, or 180 mg of ANAVEX®3-71 daily for ten days. Preliminary findings from this segment of the trial showed a dose-dependent effect of ANAVEX®3-71 on two critical EEG biomarkers in individuals with schizophrenia. Specifically, the treatment led to improvements in the 40 Hz Auditory Steady-State Response (ASSR) Inter Trial Coherence (ITC) and Resting State Alpha Power. These changes were most notable in the higher dose group, underscoring the dose-dependent pharmacodynamic impact of ANAVEX®3-71.

These encouraging results suggest central nervous system target engagement and potential therapeutic benefits of ANAVEX®3-71 for schizophrenia. The observed changes in EEG biomarkers are significant because they correlate with the positive, negative, and cognitive symptoms of schizophrenia. Schizophrenia patients often exhibit reduced neural synchrony measured by 40 Hz ASSR ITC and decreased resting state alpha power. Enhancements in 40 Hz ASSR ITC indicate better neural synchronization, which could potentially reduce auditory hallucinations and improve executive function and working memory. Similarly, increases in resting state alpha power reflect improvements in sensory and behavioral functions, potentially reducing irritability and anxiety.

Christopher U Missling, PhD, President and CEO of Anavex, expressed optimism about the initial biomarker changes observed in individuals treated with ANAVEX®3-71. He highlighted the potential of the treatment to address the broad symptom spectrum of schizophrenia, including positive, negative, and cognitive symptoms.

ANAVEX®3-71 was well tolerated in the study, with no serious adverse events reported. This oral treatment is a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator. The unique mechanism of action of ANAVEX®3-71 offers the potential to treat all symptom domains of schizophrenia without the side effects typically associated with standard antipsychotic medications. Previous studies with ANAVEX®3-71 have shown long-lasting pro-cognitive effects and behavioral improvements in animal models of neurodegenerative diseases, as well as robust safety signals in healthy volunteers.

The ongoing Part B of the placebo-controlled Phase 2 study aims to include more participants and extend the treatment duration to gather more comprehensive data on the efficacy and safety of ANAVEX®3-71 in treating schizophrenia. The results from Part B are anticipated in the first half of 2025.

Schizophrenia is a chronic and disabling mental disorder that affects nearly 24 million people worldwide, including 2.8 million in the United States. It impacts how a person thinks, feels, and behaves, presenting a range of positive symptoms (such as hallucinations and delusions), negative symptoms (such as social withdrawal and lack of enjoyment), and cognitive impairments (such as deficits in memory and decision-making). Current treatments often have limited effectiveness, and a significant portion of patients do not respond adequately or experience undesirable side effects.

Anavex Life Sciences Corp. is committed to developing novel therapeutics for neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. Their lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed various clinical trials for Alzheimer's disease and other CNS disorders. ANAVEX®3-71, targeting SIGMAR1 and M1 muscarinic receptors, shows promise as a clinical stage drug candidate with disease-modifying potential for Alzheimer's disease and other CNS conditions.