In a significant development in the fight against Alzheimer’s disease, Anavex Life Sciences Corp. (AVXL), a clinical-stage biopharmaceutical company, has presented compelling results from its Phase IIb/III trial of blarcamesine, also called Anavex 2-73, at the 2024 Alzheimer’s Association International Conference. The trial results demonstrated that blarcamesine significantly slowed clinical decline in patients with early Alzheimer’s disease.
The trial results indicated that blarcamesine, an orally administered small-molecule drug taken once daily, achieved a reduction in clinical decline after 48 weeks for those who took 50-milligram doses (a 38.5% reduction) and those who took 30-milligram doses (a 34.6% reduction) when compared to those who took a placebo.
Researchers measured the results using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, or ADAS-Cog13, a neuropsychological assessment used to measure the severity of cognitive symptoms related to dementia. The use of ADAS-Cog13 as the cognitive endpoint meets Food and Drug Admininstration guidelines for trials related to treatment of early Alzheimer’s disease.
Additionally, the trial’s key secondary endpoint, the Clinical Dementia Rating-Sum of Boxes, or CDR-SB, showed significant improvement for both dosage groups. Blarcamesine also demonstrated significant benefits in slowing brain atrophy in key regions, including a 37.6% reduction in whole brain atrophy, a 63.5% reduction in total gray matter atrophy, and a 25.1% reduction in the expansion of lateral ventricles.
The trial reported that common treatment-emergent adverse events included transient dizziness, mostly mild to moderate in severity, occurring during titration and maintenance phases. These events were manageable by adjusting the titration schedule and dosing times, as observed in the compassionate use program for blarcamesine.
Blarcamesine’s Mechanism and Advantages
Blarcamesine targets autophagy enhancement though sigma-1 receptor, or SIGMAR1 activation, to restore cellular homeostasis. This precision medicine approach enhances autophagy, a critical cellular process for clearing protein aggregates and misfolded proteins, which are hallmarks of Alzheimer’s pathology.
The drug’s unique mechanism and oral administration make it a promising candidate for broad adoption, as it does not require routine MRI monitoring and has a favorable safety profile without causing amyloid-related imaging abnormalities.
Marwan Noel Sabbagh, M.D., professor of neurology and chairman of the scientific advisory board at Anavex, emphasized the significance of these findings in a news release, noting that blarcamesine could reduce barriers within the health care ecosystem due to its convenient administration and safety profile.
Juan Carlos Lopez-Talavera, M.D., Ph.D., head of research and development at Anavex, highlighted the potential of blarcamesine to provide early Alzheimer’s patients with more time to engage in meaningful activities by slowing disease progression.
Anavex plans to submit a regulatory application to the European Medicines Agency in the fourth quarter of 2024, aiming to bring blarcamesine to a broader patient population. The trial results and the company’s precision medicine approach underscore the potential of blarcamesine to complement existing therapies and offer a novel treatment option for AD.
What’s Next for Anavex
Anavex Life Sciences continues to make significant strides in Alzheimer’s disease research. The promising results from the blarcamesine trial highlight the potential of this innovative therapy to offer hope to millions affected by this devastating disease.
Anavex is dedicated to developing novel therapeutics for neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, and schizophrenia. Blarcamesine has completed multiple clinical trials demonstrating its potential to halt or reverse the course of Alzheimer’s disease.
Anavex’s pipeline includes other promising candidates targeting the sigma-1 and muscarinic receptors, with potential applications across various central nervous system disorders.
For further details, the full presentation is available on the Investors section of Anavex’s website. The data from the Phase IIb/III trial will also be published in an upcoming peer-reviewed journal.
Note: This article discusses investigational uses of a product in development and does not intend to make conclusions about efficacy or safety. There is no guarantee that blarcamesine will successfully complete clinical development or gain health authority approval.
