Anavex Life Sciences (Nasdaq: AVXL), a clinical-stage biopharmaceutical company, has announced robust findings from its Phase 2b/3 clinical trial involving the investigational drug blarcamesine (ANAVEX®2-73). The trial, which targets patients in the early stages of Alzheimer’s disease, shows significant efficacy in slowing cognitive decline and reducing biomarkers associated with Alzheimer’s pathology. This development highlights a potential new once daily oral Alzheimer’s treatment option that could have a meaningful impact on disease management.
Key Findings from the Phase 2b/3 Clinical Trial
The Phase 2b/3 study conducted by Anavex Life Sciences enrolled 508 participants across 52 medical centers in five countries. These participants were diagnosed with early symptomatic Alzheimer’s disease, characterized by mild cognitive impairment and mild dementia. Over the course of 48 weeks, participants were randomly assigned to receive either blarcamesine (n=338) or a placebo (n=170). Blarcamesine was administered once daily in oral capsule form, positioning it as a convenient treatment option for Alzheimer’s patients.
This study successfully met its co-primary endpoints, demonstrating a statistically significant difference in the rate of cognitive decline between the treatment group and the placebo group. The key metrics used to evaluate this decline were the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). The ADAS-Cog13 score showed a mean difference of -1.783 [95% CI -3.314 to -0.251] with a significance of P=0.0226, while the CDR-SB revealed a mean difference of -0.456 [95% CI -0.831 to -0.080], with a P-value of 0.0175.
Reduction in Alzheimer’s Pathology Biomarkers
Alongside clinical improvements in cognitive function, blarcamesine also demonstrated a marked reduction in biomarkers associated with Alzheimer’s disease pathology. Specifically, there was a significant reduction in amyloid beta levels, a key protein involved in the development of Alzheimer’s disease. The plasma Aβ42/40 ratio, a recognized marker for amyloid beta pathology, increased significantly in patients receiving blarcamesine (P=0.048), reflecting the drug’s potent anti-amyloid effects.
Additionally, magnetic resonance imaging (MRI) scans revealed a reduction in brain atrophy in patients treated with blarcamesine. Whole brain volume loss was significantly reduced (P=0.0005) when compared to the placebo group, highlighting the drug’s ability to slow neurodegeneration.
Safety and Tolerability
Anavex Life Sciences also provided data regarding the safety and tolerability of blarcamesine. Common treatment-emergent adverse events included dizziness, which was transient and generally mild to moderate in severity. Dizziness occurred in 35.8% of patients during the titration phase and in 25.2% during the maintenance phase. The placebo group reported dizziness in 6.0% and 5.6% of participants during titration and maintenance, respectively. Overall, the safety profile of blarcamesine reinforces its potential as a viable once daily oral dementia treatment.
Scientific and Clinical Significance
The findings from this trial are among the first to prospectively demonstrate efficacy on biomarkers of neurodegeneration in Alzheimer’s disease patients. Dr. Marwan Noel Sabbagh, Professor of Neurology and Chairman of the Scientific Advisory Board at Anavex Life Sciences, commented on the implications of these results. “New therapies targeting Alzheimer’s disease beyond amyloid hold the potential to slow disease progression for many individuals in the early stages,” he stated. “The advantage of blarcamesine (ANAVEX®2-73) is that it is a small, oral molecule that exerts clinical benefits on cognition and neurodegeneration, and it could be appealing because of its route of administration and excellent safety profile.”
Dr. Michael Weiner, Professor of Radiology, Biomedical Imaging, and Neurology at the University of California, San Francisco, also emphasized the significance of the trial. “The ability to objectively slow markers of neurodegeneration in a clinical setting is highly encouraging and opens new avenues for Alzheimer’s treatment,” he noted.
About Anavex Life Sciences
Anavex Life Sciences Corp. is at the forefront of developing innovative therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, and other central nervous system (CNS) diseases. The company’s lead drug candidate, blarcamesine (ANAVEX®2-73), has undergone extensive clinical evaluation, including a Phase 2b/3 trial for Alzheimer’s disease and a Phase 2 proof-of-concept study in Parkinson’s disease dementia.
Blarcamesine works by restoring cellular homeostasis through the activation of sigma-1 and muscarinic receptors, offering a novel approach to treating Alzheimer’s and other CNS disorders. With its demonstrated anticonvulsant, anti-amnesic, neuroprotective, and antidepressant properties, blarcamesine holds potential for addressing a broad range of conditions beyond Alzheimer’s disease.
As Anavex Life Sciences continues to advance its research, the company remains committed to developing groundbreaking treatments for devastating diseases that affect millions of individuals worldwide.