Anavex Life Sciences Corp. has released the results from its Phase IIb/III clinical trial, revealing significant findings regarding its investigational Alzheimer’s treatment, blarcamesine (ANAVEX®2-73). This once daily oral medication has shown potential in slowing the clinical decline in patients with early-stage Alzheimer’s disease (AD), a critical step forward in addressing the unmet needs in Alzheimer’s treatment.
The trial results were presented by Dr. Marwan Noel Sabbagh, a professor of neurology and chairman of Anavex’s Scientific Advisory Board, at the 2024 Alzheimer’s Association International Conference (AAIC). The study demonstrated blarcamesine’s ability to slow clinical progression by 38.5% in patients receiving a 50 mg dosage and by 34.6% for those on a 30 mg dosage, compared to the placebo group, as measured by the ADAS-Cog13 cognitive scale. This represents the trial’s primary cognitive endpoint, meeting the March 2024 FDA guidance for early Alzheimer’s trials. Blarcamesine also impacted key biomarkers associated with Alzheimer’s disease, including amyloid-beta levels and brain atrophy.
Cognitive and Biomarker Findings
In the Phase IIb/III trial, blarcamesine was assessed using co-primary endpoints—cognitive (ADAS-Cog13) and functional (ADCS-ADL) measures. While the cognitive benefits were clearly demonstrated, the ADCS-ADL scale, used to assess functional abilities, showed a positive trend but did not reach statistical significance. Researchers noted that this scale might be less sensitive in the early stages of Alzheimer’s disease.
In addition to cognitive improvements, the trial highlighted the drug’s effects on brain atrophy, a hallmark of Alzheimer’s disease. Blarcamesine was found to slow brain atrophy in key regions, including a 37.6% reduction in whole brain atrophy and a 63.5% reduction in gray matter atrophy. These effects extend to the lateral ventricles, where a 25.1% reduction in enlargement was observed.
Notably, these findings were supported by biomarkers from the A/T/N spectrum, including improvements in the plasma Aβ42/40 ratio, a key marker in Alzheimer’s pathology. The significance of these outcomes could establish blarcamesine as a potential treatment option that addresses both cognitive symptoms and the underlying neurodegeneration associated with Alzheimer’s.
Safety and Administration
Blarcamesine, a small molecule administered orally once daily, offers a safer alternative compared to currently approved Alzheimer’s therapies. The treatment’s safety profile is noteworthy for its lack of neuroimaging-related adverse effects, such as amyloid-related imaging abnormalities (ARIA), which have been reported in some anti-amyloid treatments. Furthermore, the drug does not require routine MRI monitoring, an advantage over therapies that target amyloid plaques more directly.
In terms of tolerability, the most common adverse event reported was mild to moderate dizziness, which occurred in 35.8% of patients during titration. This side effect was generally transient and manageable by adjusting the titration schedule. Other adverse events were comparable between the treatment and placebo groups.
The once-daily oral administration of blarcamesine could also simplify treatment regimens for patients, caregivers, and healthcare providers. This convenience, combined with its safety profile, positions blarcamesine as a potentially more accessible treatment for a broader range of patients with early Alzheimer’s disease.
Future Regulatory and Clinical Outlook
Anavex Life Sciences has announced its plans to submit blarcamesine for regulatory approval in Europe, with an anticipated European Medicines Agency (EMA) submission in the fourth quarter of 2024. The company continues to explore blarcamesine’s potential in treating not only Alzheimer’s disease but also other central nervous system (CNS) disorders, including Parkinson’s disease and Rett syndrome.
Dr. Christopher U. Missling, President and CEO of Anavex Life Sciences, emphasized the significance of the trial results in addressing Alzheimer’s disease, which affects millions of people worldwide. He pointed to the unique mechanism of action that blarcamesine offers through SIGMAR1 activation and autophagy—a process that clears protein aggregates and misfolded proteins. This precision medicine approach, tailored to combat the complex pathology of Alzheimer’s, could help patients maintain cognitive function and quality of life for a longer period.
The Phase IIb/III trial results for blarcamesine underscore Anavex Life Sciences’ commitment to developing innovative therapies for neurodegenerative diseases. With its once daily oral Alzheimer’s treatment, the company offers a new approach to managing early-stage Alzheimer’s disease, potentially improving both cognitive outcomes and quality of life for patients.
As Anavex Life Sciences moves toward regulatory submission, the results from this trial may signal a significant shift in how Alzheimer’s disease is treated, particularly for patients in the early stages of the disease. The company’s dedication to providing safer, more accessible treatment options could play a crucial role in addressing the growing global burden of Alzheimer’s.
