On Blarcamesine for Alzheimer Disease, With Christopher Missling, PhD

Christopher Missling, PhD, President and CEO of Anavex Life Sciences, discussed the development of blarcamesine, a novel oral therapy for Alzheimer disease. Unlike other treatment agents targeting downstream amyloid-beta or tau pathology, blarcamesine acts upstream through sigma-1 receptor activation, restoring impaired autophagy and promoting neuronal homeostasis.¹ This broader mechanism may address the complex pathogenesis of Alzheimer disease, including genetic, environmental, and behavioral influences.

Missling added that preclinical studies demonstrated that blarcamesine prevented cognitive impairment when administered prior to disease onset, suggesting disease-modifying potential. In a phase 2b/3 randomized, placebo-controlled trial, once-daily blarcamesine not only improved clinical outcomes but also reduced brain volume loss compared with placebo.² According to the study, the drug was well tolerated, with no observed amyloid-related imaging abnormalities, intracerebral hemorrhage, cerebral edema, or drug-related deaths. These findings were recently published in the Journal of Prevention of Alzheimer Disease.²

Importantly, Missling pointed out, biomarker-driven subgroup analyses identified a precision medicine cohort, comprising up to 70% of patients who experienced near stabilization of cognitive decline and prolonged maintenance of quality of life. In an open-label extension, this translated into approximately 20 months of preserved functional status, a clinically meaningful outcome for patients and caregivers.

Missling emphasized that blarcamesine offers both efficacy and safety advantages over currently available AD therapies, while advancing the application of precision medicine into neurodegenerative disease. Regulatory discussions are ongoing globally to determine the next steps toward approval and clinical integration of this agent, Missling indicated.

Dr Missling is the president and chief executive officer of Anavex Life Sciences, a clinical-stage biopharmaceutical company developing treatments for central nervous system disorders.

References

1. Williams C, Kindermans M, Parmentier F, et al. Study of the mechanism of action of Blarcamesine (ANAVEX®2-73): Whole blood transcriptomics analysis identifies treatment impact on compensatory pathways by restoring key neurodegenerative pathways functionality, including Alzheimer’s disease pathway. J Alz Assn. 2023;19(S7):e059024.

2. Macfarlane S, Grimmer T, Teo K, et al. Blarcamesine for the treatment of early Alzheimer's disease: results from the ANAVEX2-73-AD-004 phase IIB/III trial. J Prev Alzheimers Dis. 2025;12(1):100016.