Anavex Life Sciences Corp. (Nasdaq: AVXL) has announced encouraging preliminary results from Part A of its ongoing Phase 2 clinical trial of ANAVEX3-71 for the treatment of schizophrenia. The study, a placebo-controlled, multiple ascending dose trial, demonstrated a dose-dependent effect of ANAVEX3-71 on key electroencephalography (EEG) biomarkers associated with schizophrenia. These findings suggest that ANAVEX3-71 could potentially address multiple symptom domains of schizophrenia, including positive, negative, and cognitive symptoms.
The Phase 2 study (ANAVEX3-71-SZ-001, NCT06245213) involved 16 participants who received either oral placebo, 90 mg of ANAVEX3-71 daily, or 180 mg of ANAVEX3-71 daily for 10 days. The preliminary data revealed that treatment with ANAVEX3-71 led to improvements in 40 Hz Auditory Steady-State Response (ASSR) Inter Trial Coherence (ITC) and Resting State Alpha Power, both of which were increased compared to placebo. The improvements were more pronounced in the higher dose group, indicating a dose-dependent pharmacodynamic effect.
Impact on EEG Biomarkers
The observed changes in EEG biomarkers are particularly noteworthy because they reverse known abnormalities associated with schizophrenia. Individuals with schizophrenia often exhibit reduced neural synchrony, as measured by 40 Hz ASSR ITC, and decreased resting state alpha power. Improvements in 40 Hz ASSR ITC suggest enhanced neural synchronization, which could potentially reduce auditory hallucinations and improve executive function and working memory. Increases in Resting State Alpha Power may reflect improvements in thalamocortical circuits and sensory gating, potentially leading to reduced irritability and anxiety.
A Novel Mechanism of Action
ANAVEX3-71 is an orally available dual SIGMAR1 receptor agonist and M1 positive allosteric modulator with agonistic effects. This novel mechanism of action offers the potential to treat all symptom domains of schizophrenia without the motor side effects associated with traditional antipsychotics. Christopher U Missling, PhD, President and Chief Executive Officer of Anavex, stated, "We are pleased to see an initial effect of biomarkers changing in people with schizophrenia treated with our oral M1/SIGMAR1 therapy ANAVEX3-71, which could eventually help patients address both positive, negative, and cognitive symptoms of schizophrenia. The results are encouraging for further development of ANAVEX3-71 for people with schizophrenia."
Safety and Tolerability
In Part A of the Phase 2 study, ANAVEX3-71 was well tolerated, with no serious adverse events reported. This is a crucial factor, as many existing treatments for schizophrenia are associated with significant side effects that can impact patient compliance and quality of life.
Ongoing Phase 2 Study
The ongoing Part B of the Phase 2 study includes more participants and a longer treatment duration. Anavex anticipates that this part of the study will provide more comprehensive data on the efficacy and safety of ANAVEX3-71 in schizophrenia, with data expected in the first half of 2025.
Schizophrenia: An Unmet Need
Schizophrenia is a chronic and debilitating mental illness that affects approximately 24 million people worldwide, including 2.8 million in the United States. The condition is characterized by positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). Current treatments can be effective in managing select symptoms, but approximately 34% of people do not respond to therapy, with an additional 50-60% experiencing only a partial improvement in symptoms or unacceptable side effects.
