Anavex Life Sciences Corp. (AVXL) has unveiled groundbreaking results from its Phase IIb/III clinical trial of blarcamesine, or Anavex 2-73, for treatment of early Alzheimer’s disease (AD) at the 2024 Alzheimer’s Association International Conference. The study demonstrates that this oral, once-daily treatment significantly slowed clinical decline in patients with early AD, potentially offering new hope in the fight against the devastating disorder.
The trial results, presented by Marwan Noel Sabbagh, M.D., professor of neurology and chairman of the scientific advisory board for Anavex, showed that blarcamesine reduced clinical progression after 48 weeks in patients who took 50-milligram doses (a 38.5% reduction) and 30-milligram doses (a 34.6% reduction) when compared to those who took a placebo.
Anavex Researchers Measured Results Using Three Different Assessments
The improvements for participants in the study were measured 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. ADAS-Cog13 was the prespecified primary cognitive endpoint of the study.
Importantly, the study’s design aligns with the Food and Drug Administration’s March 2024 guidance that allows a sole cognitive measure to serve as the primary endpoint for early Alzheimer’s trials. While the functional co-primary endpoint — the Alzheimer’s Disease Cooperative Study-Activities of Daily Living, or ADCS-ADL, scale — showed a positive trend, it did not reach statistical significance at 48 weeks. Researchers suggest this may be due to the ADCS-ADL scale being less sensitive for early AD patients.
The trial also met its key secondary composite endpoint, the Clinical Dementia Rating Scale-Sum of Boxes, or CDR-SB, which showed significant improvements in both the 30-milligram and 50-milligram treatment groups at 48 weeks. This endpoint is also recommended as an alternative primary endpoint for early AD in the new FDA guidance.
Blarcamesine Demonstrated Benefits in Key Biomarkers
Biomarker data further supported the clinical findings. Blarcamesine demonstrated benefits on both amyloid-beta levels and brain volume, two crucial pathological hallmarks of Alzheimer’s. The drug significantly slowed brain atrophy in key regions of interest: whole brain (a 37.6% reduction), total gray matter (a 63.5% reduction), and lateral ventricles (a 25.1% reduction).
Sabbagh expressed enthusiasm about the results in a news release. “These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” Sabbagh said. He highlighted blarcamesine’s potential advantages, including its oral administration route and favorable safety profile with no reported cases of amyloid-related imaging abnormalities).
Blarcamesine’s unique mechanism of action, which targets the improvement of autophagy (a key cellular clearance mechanism), positions it as a potentially complementary treatment to currently approved anti-beta amyloid monoclonal antibody drugs. This approach could address protein aggregates and misfolded proteins across the Alzheimer’s disease continuum.
Anavex Trial Participants Report Mild-to-Moderate Side Effects
The safety profile of blarcamesine appears promising, with the most common treatment-emergent adverse event being dizziness. This side effect was generally transient and mild to moderate in severity. Researchers noted that adjusting the titration schedule to a slower pace and administering the drug at nighttime could help manage these events, as observed in the blarcamesine compassionate use program.
“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide,” Christopher U. Missling, Ph.D., president and CEO of Anavex, said in the news release. “The findings from this and previous studies with blarcamesine in Alzheimer’s disease further strengthen our belief in the potential of addressing the complex pathology in Alzheimer’s disease through an upstream precision medicine compensatory process, autophagy through SIGMAR1 activation.”
The positive results from this landmark trial have paved the way for Anavex to move forward with regulatory submissions. The company expects to submit an application to the European Medicines Agency in the fourth quarter of 2024.
These findings represent a significant step forward in AD research and treatment. Blarcamesine’s ability to slow clinical decline and affect underlying disease pathology offers new hope for patients and their families. As a small-molecule drug with once-daily oral administration, it could potentially reduce barriers to treatment access and provide a more convenient option for early AD patients.
Anavex continues to research other neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. The company’s pipeline includes investigations into Parkinson’s disease, Rett syndrome, and schizophrenia, among others.
While these results are promising, it’s important to note that blarcamesine is still an investigational drug. Further research and regulatory reviews will be necessary to fully establish its efficacy and safety profile.
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.
