Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial

Blarcamesine, demonstrating a safety profile with no associated neuroimaging adverse events, significantly slowed clinical progression by 36.3% at 48 weeks with blarcamesine group as well as the individual 30 mg (by 34.6%) and 50 mg (by 38.5%) blarcamesine groups vs. placebo on the prespecified primary cognitive endpoint ADAS-Cog13. The prespecified secondary endpoint CDR-SB, which is used as the sole primary endpoint in recent successful AD drug submissions, is significantly improved at Week 48 with blarcamesine relative to placebo. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Aβ42/40-ratio and reduction of whole brain atrophy. Additionally, the prespecified SIGMAR1 gene variant subgroup analysis confirmed beneficial clinical effect of blarcamesine group through upstream SIGMAR1 activation - subjects with the common SIGMAR1 wild-type gene (excluding carriers of the mutated SIGMAR1 rs1800866 variant) experienced an even greater significant clinical benefit with slowed clinical progression by 49.8% at 48 weeks on the prespecified primary cognitive endpoint ADAS-Cog13. Oral once daily blarcamesine could represent a novel treatment in early AD and be complementary or alternative to anti-beta amyloid drugs.

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Publication Details

Journal
The Journal of Prevention of Alzheimer s Disease
Published
2025-01-01
DOI
https://doi.org/10.1016/j.tjpad.2024.100016
Citations
32
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
37.26
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article

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial

Samuel Connell, Alex Thompson, Stephen Macfarlane, Peter Drysdale et al.
32 citations
The Journal of Prevention of Alzheimer s Disease
Alzheimer's disease research and treatments
37.26
article

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial

Samuel Connell, Alex Thompson, Stephen Macfarlane, Peter Drysdale, Jens Wiltfang, Jennifer Grunfeld, Terence John O'Brien, Stephen Pasternak, Josephine Emer MacSweeney, Eric Edward Smith, Maria Carmela Tartaglia, Oliver Peters, Timo Grimmer, Nicholas Mannering, Alexandre Henri‐Bhargava, Richard Perry, Elizabeth Gordón, Mark Woodward, Niels D. Prins, Malathy Munisamy, Susan Kurrle, Amy G. Brodtmann, Rosalyn Lai, Aliya Asher, Neel S. Bhatt, Sterre Malou Rutgers, Thomas Jubault, Lutz Froelich, Craig Evans, Stephen Pearson, Saghira Malik Sharif, Ging‐Yuek Robin Hsiung, Andrew Frank, Paweł Tacik, Luca M. Villa, Alastair Mander, Christopher U. Missling, Chris Kalafatis, Ken Teo, Dávid Barton, Nicolas Guizard, P. L. J. Dautzenberg, Simon J.G. Lewis, Howard Chertkow, Patrick Oschmann, Sneha Bharadwaj, Walter E. Kaufmann, Marwan N. Sabbagh, Sharon Cohen, Jennifer Lynch, Kun Jin, Jonathan Sturm, Robert S. Brittain, Bruce J. Brew, J. David Ingram, A. Tucker, Philip Morris, Vivek Krishna, C Short, William R Chezem
article en
32 citations

Abstract

Blarcamesine, demonstrating a safety profile with no associated neuroimaging adverse events, significantly slowed clinical progression by 36.3% at 48 weeks with blarcamesine group as well as the individual 30 mg (by 34.6%) and 50 mg (by 38.5%) blarcamesine groups vs. placebo on the prespecified primary cognitive endpoint ADAS-Cog13. The prespecified secondary endpoint CDR-SB, which is used as the sole primary endpoint in recent successful AD drug submissions, is significantly improved at Week 48 with blarcamesine relative to placebo. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Aβ42/40-ratio and reduction of whole brain atrophy. Additionally, the prespecified SIGMAR1 gene variant subgroup analysis confirmed beneficial clinical effect of blarcamesine group through upstream SIGMAR1 activation - subjects with the common SIGMAR1 wild-type gene (excluding carriers of the mutated SIGMAR1 rs1800866 variant) experienced an even greater significant clinical benefit with slowed clinical progression by 49.8% at 48 weeks on the prespecified primary cognitive endpoint ADAS-Cog13. Oral once daily blarcamesine could represent a novel treatment in early AD and be complementary or alternative to anti-beta amyloid drugs.

The Journal of Prevention of Alzheimer s DiseaseVol. 12(1)
Island Health (CA), University of British Columbia Hospital (CA), The University of Sydney (AU), Imperial College Healthcare NHS Trust (GB), King's College London (GB), Toronto Western Hospital (CA), University Hospital Bonn (DE), Parks Victoria (AU), Hornsby Ku-ring-gai Hospital (AU), Bayreuth Medical Center (DE), TUM Klinikum (DE), St Vincent's Hospital Sydney (AU), Queen Elizabeth Hospital (AU), Metropolitan Arts Centre (GB), St Vincent’s Private Hospital Sydney (AU), Dementia Collaborative Research Centres (AU), Central Institute of Mental Health (DE), Cambridge Cognition (United Kingdom) (GB), Bruyère (CA), Technical University of Munich (DE), Charité - Universitätsmedizin Berlin (DE)
Good health and well-being
Openalex Percentile: Top 0%
Alzheimer's disease research and treatments
37.26
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