Anavex presents new data from blarcamesine study at CTAD conference

Anavex (AVXL) presented new data from the Phase IIb/III study showing that blarcamesine, once daily orally, demonstrates pre-specified clinical efficacy through upstream SIGMAR1 activation. Clinical data confirmed the mechanism of action, ort MoA, by pre-specified SIGMAR1 gene analysis in people with early Alzheimer’s disease, or AD. The data were presented by Marwan Noel Sabbagh, professor of Neurology at Barrow Neurological Institute and chairman of the Anavex Scientific Advisory Board at the Clinical Trials on Alzheimer’s Disease, or CTAD conference, which is taking place October 29 – November 1, in Madrid, Spain. SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis. In Alzheimer’s disease patients, mutations of genes have generally been identified as disease risk factors. Likewise, impaired SIGMAR1 function leads to potential suboptimal function. Hence, patients who carry the non-mutated, common SIGMAR1 wild type 1 gene, are expected to have stronger beneficial response to blarcamesine than patients with a SIGMAR1 mutation, who nevertheless also benefited from treatment. This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint ADAS-Cog13 in the ITT analysis. This signal was even stronger in the pre-specified common SIGMAR1 wild type, or WT, group with slowed clinical progression by 49.8% at 48 weeks in the active group vs. placebo, respectively. Equal analysis with CDR-SB led to comparable consistent results. Overall, blarcamesine, a small molecule administered orally once daily, demonstrated clinically meaningful improvement over 48 weeks with primary endpoint ADAS-Cog13 score being larger than two points. This suggests superior numerical clinical efficacy compared to approved therapies while also slowing neurodegeneration in early AD patients. Blarcamesine’s safety profile indicates not requiring routine MRI monitoring, and given its differentiated mechanism of action, could represent a novel treatment that could be complementary or an alternative to anti-beta amyloid monoclonal antibody drugs.