Anavex Life Sciences Corp. (Nasdaq: AVXL) announced positive results from its Phase IIb/III clinical trial of blarcamesine (ANAVEX®2-73) for the treatment of early Alzheimer's disease. The data, presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference in Madrid, Spain, demonstrated that once-daily, oral blarcamesine achieved pre-specified clinical efficacy through upstream SIGMAR1 activation.
The study confirmed the drug's mechanism of action (MoA) via pre-specified SIGMAR1 gene analysis in patients with early Alzheimer's. Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of the Anavex Scientific Advisory Board, presented the findings.
Impact on Clinical Progression
Over a 48-week period, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint, ADAS-Cog13 [LS mean ADAS-Cog13 difference of -2.027; P=0.008] in the ITT analysis. In a pre-specified group with the common SIGMAR1 wild type (WT) gene, the effect was even more pronounced, with a 49.8% reduction in clinical progression compared to placebo (LS mean ADAS-Cog13 difference of -2.317; P=0.015). Comparable results were observed with CDR-SB analysis.
SIGMAR1 Activation and Autophagy
Blarcamesine activates SIGMAR1, an integral membrane protein, which in turn initiates autophagy, a cellular process that restores homeostasis by clearing protein aggregates and misfolded proteins. According to Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex, this novel upstream mechanism of action is a key advantage of blarcamesine.
Potential Advantages over Existing Therapies
Blarcamesine, a small molecule administered orally once daily, demonstrated clinically meaningful improvement over 48 weeks, with the primary endpoint ADAS-Cog13 score being more than 2 points larger than placebo. This suggests potentially superior clinical efficacy compared to currently approved therapies, while also slowing neurodegeneration in early Alzheimer's patients. The safety profile of blarcamesine suggests that routine MRI monitoring may not be required. Its unique mechanism of action could make it a complementary or alternative treatment to anti-beta amyloid monoclonal antibody drugs.
Management Perspective
Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex, stated that the clinically meaningful study results offer the potential for patients and their families to have a better and longer quality of life. He also noted that the scalable and convenient features of blarcamesine could reduce barriers within the healthcare ecosystem and provide broader access to a diverse population with early Alzheimer's disease.
Anavex is on track for regulatory submission of blarcamesine in Europe (EMA) in the current quarter of 2024.
