Anavex Life Sciences' blarcamesine (ANAVEX®2-73) has demonstrated significant slowing of clinical decline in patients with early Alzheimer's disease in a Phase IIb/III trial. The oral, once-daily drug showed a good safety profile and no associated neuroimaging adverse events. These findings, presented at the 2024 Alzheimer's Association International Conference (AAIC), suggest blarcamesine could be a promising treatment option for early Alzheimer's.
Clinical Efficacy and Biomarker Impact
Blarcamesine significantly slowed clinical progression by 38.5% and 34.6% at 48 weeks in the 50 mg and 30 mg groups, respectively, compared to placebo, based on the prespecified primary cognitive endpoint ADAS-Cog13 (Alzheimer's Disease Assessment Scale-cognitive subscale 13). The trial also met the key secondary composite endpoint CDR-SB (Clinical Dementia Rating-Sum of Boxes) at both 30 mg and 50 mg at Week 48. These results align with the FDA's March 2024 guidance for early Alzheimer's trials, which allows a sole cognitive measure to serve as the primary endpoint.
"These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration," said Dr. Marwan Noel Sabbagh, Professor of Neurology at Barrow Neurological Institute and Chairman of the Scientific Advisory Board.
The study also revealed benefits on biomarkers from the A/T/N spectrum, including 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 grey matter by 63.5%, and lateral ventricles by 25.1%.
Safety and Tolerability
The safety profile of blarcamesine was notable, with no neurological tissue damage such as hemorrhage or Amyloid-related imaging abnormalities (ARIA) observed. Common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity. These events were manageable by adjusting the titration schedule.
Mechanism of Action and Potential Benefits
Blarcamesine is a small molecule administered orally once daily. It is designed to improve autophagy, a key clearance mechanism that removes protein aggregates and misfolded proteins, through SIGMAR1 activation. This mechanism of action differentiates it from currently approved anti-beta amyloid monoclonal antibody drugs and could potentially offer a complementary treatment approach.
Regulatory Pathway and Future Directions
Anavex Life Sciences anticipates a full regulatory submission of blarcamesine in Europe (EMA) in Q4 2024. This submission marks a significant step toward potentially making blarcamesine available to patients with early Alzheimer's disease.
"The study results provide the potential for people with more time to engage in meaningful activities," said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex.
The company believes that blarcamesine's scalable and convenient features could reduce crucial barriers within the healthcare ecosystem for Alzheimer's disease and provide broader access to a diverse population with early Alzheimer's disease.
