Cassava Announces Publication of Peer-Reviewed Phase 3 Results for Simufilam in Alzheimer’s Disease in the Journal of Prevention of Alzheimer’s Disease

Core Insights - The studies RETHINK-ALZ and REFOCUS-ALZ did not meet their pre-specified co-primary, secondary, or exploratory biomarker endpoints, but exploratory post-hoc analyses provided informative insights regarding the treatment effects of simufilam in specific patient subgroups [1][2][5] Study Overview - RETHINK-ALZ (NCT04994483) randomized 804 participants, while REFOCUS-ALZ (NCT05026177) included 1,125 patients, both focusing on mild to moderate Alzheimer's disease [3][9] - The trials were multi-center, double-blinded, placebo-controlled studies designed to evaluate the safety and efficacy of simufilam compared to placebo [9] Safety and Efficacy Findings - Simufilam demonstrated a favorable safety profile in the studies, with detailed safety observations reported [1][4] - In the predefined mild subgroup (MMSE score 21-27), simufilam (100 mg) was associated with slower cognitive decline compared to placebo at various weeks, with nominal significance at p = 0.01, 0.01, 0.02, 0.02, and 0.02 for Weeks 4, 28, 40, 52, and 64 respectively [5][6] Exploratory Analyses - Exploratory findings indicated potential treatment differences in the mild subgroup, with a prespecified pooled analysis showing nominal significance at p < 0.01 for Weeks 4 and 28 [5][6] - A post hoc analysis using a plasma p-tau181 cutoff of ≥ 67 showed significant differences in cognitive decline at Weeks 4, 28, and 40 (p = 0.03, 0.001, 0.006 respectively) [6] Future Directions - The company has discontinued the development of simufilam for Alzheimer's disease but aims to leverage the safety observations for ongoing development in TSC-related epilepsy [3][4][8] - Cassava Sciences plans to initiate a proof-of-concept study for simufilam in TSC-related epilepsy, collaborating with leading investigators [4][12]