Anavex presents results from Phase IIb/III trial of Blarcamesine

Anavex Life Sciences presented comprehensive results from the Phase IIb/III study showing that blarcamesine, once daily orally, significantly slowed clinical decline in people with early Alzheimer’s disease. The data were presented at the 2024 Alzheimer’s Association International Conference. Blarcamesine significantly slowed clinical progression by 38.5% and 34.6% at 48 weeks in 50 mg and 30 mg groups vs. placebo, respectively, on the prespecified primary cognitive endpoint ADAS-Cog13. As specified in the March 2024 FDA Guidance for Early AD, a sole cognitive measure can serve as the primary endpoint for early Alzheimer’s trials.1 The protocol was designed with ADAS-Cog13 and ADCS-ADL as co-primary endpoints. The functional co-primary endpoint, ADCS-ADL, was trending positive but did not reach significance at Week 48. A possible explanation is that the ADCS-ADL scale is designed for AD with overt dementia and is less sensitive for early AD.2 The prespecified key secondary composite endpoint CDR-SB, also recommended as an alternative primary endpoint for early AD in the new FDA guidance, is significant at both 30 mg and 50 mg at Week 48. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Abeta42/40-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%. Blarcamesine, a small molecule administered orally once daily, demonstrated numerically superior clinical efficacy 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 to the currently approved anti-beta amyloid monoclonal antibody drugs. For the primary endpoint ADAS-Cog13, blarcamesine is significantly better than placebo for both 50 mg at 48 weeks and for 30 mg blarcamesine dosage groups at 48 weeks. The key secondary endpoint CDR-SB was significantly improved vs. placebo in both 50 mg and 30 mg assigned dose groups. CGI-I was significantly improved in both 50 mg and 30 mg groups.