Drug Candidate for Schizophrenia, Alzheimer Disease Approved to Initiate Phase 2 Trial in Q2 2024

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A placebo-controlled phase 2 trial for a therapeutic candidate aimed at addressing neurodegenerative and neurodevelopmental disorders has been approved by the US Food & Drug Administration (FDA) to initiate in the second quarter of 2024, following positive initial phase 1 results in healthy trial volunteers.

The therapeutic candidate—Anavex 3-71 (formerly known as AF710B)—aims to address multiple neurodevelopmental and neurodegenerative disorders including Alzheimer disease, Parkinson disease, Rett syndrome, and schizophrenia. It functions as a dual SIGMAR1 receptor agonist and M1 positive allosteric modulator, offering a novel mechanism of action. This mechanism of action has the potential to treat various symptom domains of schizophrenia—positive, negative, and cognitive—while avoiding the adverse effects associated with other antipsychotics.¹

The dual synergistic mechanism of action demonstrated by Anavex 3-71 has shown promising results in animal models of neurodegenerative diseases, displaying long-lasting, pro-cognitive effects and behavioral improvements. The compound has also exhibited the ability to prevent cognitive decline in an animal model of Alzheimer disease.¹

Recent genetic research has identified connections between schizophrenia and Alzheimer disease, suggesting shared mechanisms between the 2 disorders. Notably, a successful trial of Karuna Therapeutics’ dual M1/M4 muscarinic receptor agonist, KarXT (xanomeline-trospium), in individuals with schizophrenia has shown efficacy in treating both positive and negative symptoms,¹ leading the FDA to grant the treatment a Prescription Drug User Fee Act (PDUFA) date of September 26, 2024.² Muscarinic agonists have been explored in the context of Alzheimer disease and schizophrenia in previous studies.¹

“Schizophrenia is a serious mental illness affecting 24 million people worldwide,” said Christopher U. Missling, PhD, president and chief executive officer of Anavex Life Sciences Corp, developer of Anavex 3-71, in a press release. “While current antipsychotic therapies can be effective in managing positive symptoms, like hallucinations and delusions, they may not fully address persistent negative symptoms or cognitive difficulties. Often, available treatments are limited by side effects, eg, movement disorders, sedation, weight gain, and other metabolic side effects.”

Research shows that approximately 30% of individuals with schizophrenia to not respond to therapies, and additional 50% either experience intolerable adverse effects or only experience partial improvement in their symptoms.¹

To address all of this, Anavex aims to leverage its Precision Medicine Platform by studying Anavex 3-71 alongside blarcamesine (Anavex 2-73), an orally available drug candidate that reestablishes cellular homeostasis by targeting muscarinic and SIGMAR1 receptors. The company is studying this combination of drug candidates in order to offer potential treatment options for Alzheimer disease and schizophrenia.¹

Anavex 3-71, with its selective SIGMAR1 receptor activity, presents a new pharmacological approach to address disruptions to neuronal homeostasis observed in individuals with schizophrenia. This is expected to complement existing treatments that do not comprehensively cover all symptom domains in schizophrenia.¹

The placebo-controlled phase 2 study, Anavex 3-71-SZ-001, will consist of 2 parts, investigating multiple ascending doses in individuals with schizophrenia, followed by a 28-day treatment period in a larger cohort. Standard clinical outcome measures for schizophrenia, such as the Positive and Negative Symptoms Scale (PANSS) and novel electrophysiological biomarkers identified by the ERP Biomarker Qualification Consortium, will be utilized in the study.¹

“We are excited to build on our diverse Precision Medicine Platform and to now also study Anavex 3-71 as a novel pharmacological approach to potentially provide a new schizophrenia treatment option for patients and their physicians,” Missling said in a press release.

Stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders at psychiatrictimes.com.

Note: This article was prepared with the assistance of ChatGPT.

References

1. Anavex Life Sciences announces U.S. phase 2 clinical trial of Anavex®3071 in schizophrenia. Anavex Life Sciences Corp. News release. January 16, 2024. Accessed January 25, 2024. https://www.anavex.com/post/anavex-life-sciences-announces-phase-2-clinical-trial-anavex-3-71-schizophrenia

2. O’Brien E. FDA accepts NDA, grants PDUFA data for investigational schizophrenia treatment. Psychiatric Times. November 30, 2023. Accessed January 25, 2024. https://www.psychiatrictimes.com/view/fda-accepts-nda-grants-pdufa-date-for-investigational-schizophrenia-treatment