Anavex Life Sciences recently presented comprehensive results from a Phase IIb/III study showing that its compound blarcamesine, or Anavex 2-73, significantly slowed clinical decline in people with early Alzheimer’s disease. Marwan Noel Sabbagh, M.D., professor of neurology and chairman of the scientific advisory board for Anavex, presented the data at the 2024 Alzheimer’s Association International Conference.
Anavex is a clinical-stage biopharmaceutical company that is developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including AD, Parkinson’s disease, Rett syndrome, schizophrenia and other central nervous system diseases.
Blarcamesine is a once-daily oral medication. The small-molecule compound demonstrated numerically superior clinical efficacy when compared to approved therapies while also slowing neurodegeneration in early AD patients. Blarcamesine’s safety profile indicates that it does not require routine MRI monitoring. Given its differentiated mechanism of action, it represents a novel treatment that could be complementary to currently approved anti-beta amyloid monoclonal antibody drugs.
The Anavex Blarcamesine Phase IIb/III Study Findings
The Phase IIb/III study demonstrated that blarcamesine significantly slowed 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. 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.
Under the March 2024 guidance from the Food and Drug Administration , a sole cognitive measure can serve as the primary endpoint for early Alzheimer’s trials. The protocol was designed with ADAS-Cog13 and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living, or ADCS-ADL, scale as co-primary endpoints. The functional co-primary endpoint, ADCS-ADL, was trending positive but did not reach significance at 48 weeks. A possible explanation is that the ADCS-ADL scale is designed for AD with overt dementia and is less sensitive for early AD.
The prespecified key secondary composite endpoint — the Clinical Dementia Rating Scale-Sum of Boxes, or CDR-SB — is recommended as an alternative primary endpoint for early AD in the new FDA guidance. It showed significant improvements for trial participants in both the 30-milligram and 50-milligram groups after 48 weeks.
The findings are supported by biomarkers from the amyloid-tau-neurodegeneration spectrum, a biological framework that categorizes people based on AD biomarkers rather than clinical symptoms. These included plasma Aβ42/40-ratio and reduction of brain atrophy. Blarcamesine significantly slowed brain atrophy in key regions of interest, including the whole brain by 37.6%, total gray matter by 63.5%, and lateral ventricles by 25.1%.
Industry Reaction and Company Feedback
In a news release about the clinical trial results, Sabbagh said, “These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration.”
“The advantage of blarcamesine is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and good comparative safety profile with no [amyloid-related imaging abnormalities],” Sabbagh said. “We believe the scalable and convenient features of blarcamesine could reduce crucial barriers within the currently complex healthcare ecosystem for Alzheimer’s disease and provide broader access to a diverse population with early Alzheimer’s disease.”
Juan Carlos Lopez-Talavera, M.D., Ph.D., head of research and development for Anavex, said that “Anavex’s precision medicine approach, tailored to improving autophagy, a key clearance mechanism that removes protein aggregates and misfolded proteins across the Alzheimer’s disease continuum, uniquely positions the company to develop innovative solutions for patients and their families.”
He added that the study results “provide the potential for people with more time to engage in meaningful activities.” He said Anavex plans to make a full regulatory submission of blarcamesine to the Europe Medicines Agency in the fourth quarter of 2024.
In the respective safety population, common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity.
Christopher U. Missling, Ph.D., president and chief executive officer of Anavex, said the trial results support Anavex’s approach to treating early AD.
“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide,” he said. “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.”
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.
