Anavex Life Sciences Corp. has unveiled promising results from its landmark Phase IIb/III clinical trial of blarcamesine (ANAVEX®2-73), a potential once daily oral dementia treatment for early Alzheimer’s disease. The findings, presented at the 2024 Alzheimer’s Association International Conference (AAIC), demonstrate significant slowing of clinical decline in patients with early Alzheimer’s disease.
The study, conducted by Anavex Life Sciences, evaluated blarcamesine, an orally administered small molecule, in two dosage groups: 30 mg and 50 mg. Both treatment arms showed notable efficacy compared to placebo, with the 50 mg group demonstrating a 38.5% reduction in clinical progression and the 30 mg group showing a 34.6% reduction at 48 weeks.
The primary cognitive endpoint, ADAS-Cog13, showed statistically significant improvements for both dosage groups. The 50 mg group achieved a score of -2.149 (p = 0.021), while the 30 mg group reached -1.934 (p = 0.026) at 48 weeks compared to placebo. These results align with the March 2024 FDA Guidance for Early AD, which allows a sole cognitive measure to serve as the primary endpoint in early Alzheimer’s trials.
While the functional co-primary endpoint, ADCS-ADL, showed a positive trend, it did not reach statistical significance at Week 48. Researchers suggest this may be due to the scale’s design, which is more suitable for overt dementia than early Alzheimer’s disease.
The key secondary composite endpoint, CDR-SB, recommended as an alternative primary endpoint for early AD in recent FDA guidance, demonstrated significance for both dosage groups at Week 48. The 50 mg group achieved -0.465 (p = 0.045), and the 30 mg group reached -0.502 (p = 0.020).
Anavex Life Sciences’ blarcamesine also showed promising results in biomarkers associated with Alzheimer’s disease pathology. The treatment significantly slowed brain atrophy in key regions, including a 37.6% reduction in whole brain atrophy, a 63.5% reduction in total grey matter atrophy, and a 25.1% reduction in lateral ventricle expansion.
Dr. Marwan Noel Sabbagh, Professor of Neurology at Barrow Neurological Institute and Chairman of the Scientific Advisory Board, emphasized the excitement surrounding these data, particularly the objective slowing of neurodegeneration markers. He highlighted blarcamesine’s potential advantages, including its oral administration route and favorable safety profile.
Notably, neuroimaging evaluations conducted during the Phase IIb/III study revealed no neurological tissue damage, such as hemorrhage or Amyloid-related imaging abnormalities (ARIA), which have been associated with other anti-amyloid targeted therapies.
The safety profile of blarcamesine suggests that routine MRI monitoring may not be necessary, potentially reducing barriers to treatment access. Common treatment-emergent adverse events included transient dizziness, which was mostly mild to moderate and manageable through adjusted titration schedules and nighttime dosing.
Anavex Life Sciences’ precision medicine approach focuses on improving autophagy, a key clearance mechanism for protein aggregates and misfolded proteins across the Alzheimer’s disease continuum. This unique positioning may allow for the development of innovative solutions for patients and their families.
Dr. Juan Carlos Lopez-Talavera, Head of Research and Development at Anavex Life Sciences, emphasized the potential impact of blarcamesine on patients’ quality of life, stating that the study results could provide people with more time to engage in meaningful activities.
Anavex Life Sciences plans to submit a full regulatory application for blarcamesine to the European Medicines Agency (EMA) in Q4 2024.
Christopher U. Missling, Ph.D., President and CEO of Anavex Life Sciences, expressed gratitude to study participants and reiterated the company’s commitment to addressing the high unmet need in Alzheimer’s disease treatment with a potentially new, convenient, orally available option.
As Anavex Life Sciences continues to advance blarcamesine through the regulatory process, the medical community eagerly awaits further developments in this promising once daily oral dementia treatment. The company’s focus on targeting complex Alzheimer’s disease pathology through an upstream precision medicine approach may offer new hope for millions of patients worldwide affected by this devastating neurodegenerative disorder.
