Anavex Life Sciences Corp. has announced positive topline results from two clinical studies of ANAVEX®3-71, marking significant progress for the experimental treatment targeting schizophrenia and other central nervous system disorders. The company reported successful outcomes from both a Phase 2 schizophrenia study and a Phase 1b formulation development trial.
Phase 2 Schizophrenia Study Meets Primary Endpoint
The placebo-controlled Phase 2 clinical study (ANAVEX3-71-SZ-001) successfully achieved its primary endpoint, demonstrating that ANAVEX®3-71 was safe and well-tolerated in adults with schizophrenia on stable antipsychotic medication. The safety profile remained consistent with previous studies in healthy volunteers, with no serious treatment-emergent adverse events (TEAEs) and no severe TEAEs reported in either Part A or Part B of the study.
In Part A of the study, which evaluated 30mg and 60mg doses against placebo, only one participant (16.7%) in the 30mg group experienced a treatment-emergent adverse event, while no participants in the 60mg or placebo groups reported TEAEs. Part B, focusing on the 60mg dose, showed comparable safety between ANAVEX®3-71 (39.3% experiencing TEAEs) and placebo (48.1% experiencing TEAEs), with no participants discontinuing due to adverse events in the treatment group.
Encouraging Biomarker Trends Support Continued Development
Beyond meeting the primary safety endpoint, secondary and exploratory analyses revealed promising trends in several outcome measures. The study demonstrated positive trends in objective electroencephalography (EEG) and event-related potential (ERP) biomarkers of schizophrenia.
Notably, neuroinflammatory biomarker assessments showed that glial fibrillary acidic protein (GFAP), a marker of neuroinflammation, was reduced in participants receiving ANAVEX®3-71 compared to placebo. GFAP serves as a marker of astrocyte reactivity to neuronal injury and disease, with established relevance to both neuropsychiatric and neurodegenerative disorders.
"We are encouraged that our ANAVEX3-71-SZ-001 study aligns with our expectations for safety and tolerability," said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. "We believe we are well-positioned to advance a competitive candidate into future studies aimed at addressing the ongoing and unmet medical needs of individuals living with schizophrenia and neurodegenerative diseases."
Superior Once-Daily Formulation Developed
Concurrently, Anavex announced successful development of a once-daily oral tablet formulation for ANAVEX®3-71 through the ANAVEX3-71-002 trial. The completed open-label, randomized study evaluated the pharmacokinetics and safety of immediate- and modified release formulations in healthy male and female adults 18 years or older.
The once-daily modified-release oral tablet exhibits superior pharmacokinetics compared to the current immediate-release oral capsule, enabling once-daily dosing while maintaining a safety profile consistent with prior ANAVEX®3-71 studies.
"We are pleased to see that our latest ANAVEX®3-71 formulation study meets our expectations for safety and tolerability," said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. "We believe that with the preferred modified release formulation, we can advance a competitive molecule into future studies, with the goal of addressing the present and persistent medical needs of people living with schizophrenia and neurodegenerative disorders."
Novel Mechanism Addresses Unmet Medical Need
ANAVEX®3-71 (formerly AF710B) is a 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 (positive, negative, and cognitive) of schizophrenia without the side effects of standard of care antipsychotics.
The drug candidate has previously been studied in healthy volunteers and represents a significant advancement in addressing the limitations of current schizophrenia treatments. Approximately 34% of people with schizophrenia do not respond to therapy, with an additional 50-60% experiencing only partial improvement in symptoms or unacceptable side effects.
Clinical Significance for CNS Disorders
The positive results support ANAVEX®3-71's potential as a disease-modifying treatment that could address underlying pathophysiology beyond symptomatic control. The reduction in neuroinflammatory markers suggests potential benefits that may become more pronounced with longer treatment durations.
"We believe this study is a manifestation of Anavex's continued platform expansion aiming to provide potential beneficial effect for patients with oral compounds," said Missling. "The positive safety profile and encouraging biomarker trends support the continued development of ANAVEX®3-71 as a potential treatment for CNS disorders that could address underlying pathophysiology beyond symptomatic control."
Schizophrenia affects nearly 24 million people worldwide, including 2.8 million people in the U.S., and 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).
