Anavex Life Sciences Corp. has announced promising results from its Phase IIb/III clinical trial of blarcamesine (ANAVEX®2-73), an oral Alzheimer’s disease medication, at the 2024 Alzheimer’s Association International Conference. The study demonstrated that blarcamesine, administered once daily, significantly slowed clinical decline in patients with early Alzheimer’s disease.
The trial results, presented by Dr. Marwan Noel Sabbagh, Professor of Neurology at Barrow Neurological Institute and Chairman of Anavex Life Sciences’ Scientific Advisory Board, showed that blarcamesine reduced clinical progression by 38.5% and 34.6% at 48 weeks in the 50 mg and 30 mg treatment groups, respectively, compared to placebo. These improvements were measured using the ADAS-Cog13 scale, which served as the prespecified primary cognitive endpoint.
Anavex Life Sciences’ blarcamesine is a small molecule that targets the sigma-1 receptor (SIGMAR1) and muscarinic receptors. This mechanism of action is believed to enhance autophagy, a cellular process that removes protein aggregates and misfolded proteins associated with Alzheimer’s disease pathology.
The study design included ADAS-Cog13 and ADCS-ADL as co-primary endpoints. While the ADAS-Cog13 results were statistically significant, the functional co-primary endpoint ADCS-ADL showed a positive trend but did not reach statistical significance at Week 48. Researchers suggest this may be due to the ADCS-ADL scale’s lower sensitivity in early Alzheimer’s disease patients.
Importantly, the trial also assessed a key secondary composite endpoint, CDR-SB, which showed significant improvements in both the 30 mg and 50 mg treatment groups at Week 48. This endpoint is recommended as an alternative primary endpoint for early Alzheimer’s disease in recent FDA guidance.
The efficacy of blarcamesine was further supported by biomarker data. The drug demonstrated positive effects on plasma Aβ42/40 ratio and reduced brain atrophy. Specifically, blarcamesine slowed brain atrophy by 37.6% in whole brain measurements, 63.5% in total grey matter, and 25.1% in lateral ventricles.
Dr. Sabbagh emphasized the potential advantages of blarcamesine as an oral Alzheimer’s disease medication, noting its clinical benefits on cognition and neurodegeneration, coupled with a favorable safety profile. Unlike some anti-amyloid therapies, blarcamesine did not show evidence of neurological tissue damage such as hemorrhage or Amyloid-related imaging abnormalities (ARIA) in neuroimaging evaluations.
The safety profile of blarcamesine suggests that routine MRI monitoring may not be necessary, potentially simplifying treatment administration. The most common treatment-emergent adverse event was dizziness, which was generally mild to moderate and transient. This side effect appeared manageable through adjusted titration schedules and nighttime dosing.
Anavex Life Sciences plans to submit a full regulatory application for blarcamesine to the European Medicines Agency (EMA) in Q4 2024. The company believes that the oral administration and safety profile of blarcamesine could reduce barriers to treatment access for a diverse population of early Alzheimer’s disease patients.
Dr. Christopher U. Missling, President and CEO of Anavex Life Sciences, expressed optimism about the potential of blarcamesine to address the complex pathology of Alzheimer’s disease through its unique mechanism of action. He emphasized the company’s commitment to developing a convenient, orally available treatment option for Alzheimer’s disease patients.
The positive results from this landmark trial position Anavex Life Sciences as a potential leader in the development of oral Alzheimer’s disease medications. By targeting upstream processes like autophagy through SIGMAR1 activation, blarcamesine represents a novel approach to treating Alzheimer’s disease that could complement existing therapies.
As the global burden of Alzheimer’s disease continues to grow, the development of effective, well-tolerated, and easily administered treatments remains a critical unmet need. The progress made by Anavex Life Sciences with blarcamesine offers hope for patients and their families, potentially providing more time for meaningful engagement and activities in the early stages of the disease.
While these results are promising, it’s important to note that blarcamesine is still an investigational drug. Further research and regulatory review will be necessary to fully establish its efficacy and safety profile. The medical community and patients alike will be eagerly awaiting the publication of the full trial data in a peer-reviewed journal and the outcome of upcoming regulatory submissions.