Clinical-stage biotech firm Cassava Sciences, Inc., dedicated to pioneering innovative treatments for Alzheimer’s disease (AD) dementia, has disclosed that its phase 3 study, ReThink-ALZ, evaluating simufilam for mild-to-moderate AD, did not achieve its pre-set co-primary, secondary, and exploratory biomarker objectives. The main goals were to evaluate cognitive and functional changes from baseline to week 52’s double-blind period, using ADAS-COG12 and ADCS-ADL scales against placebo. Simufilam displayed a consistently favorable safety profile.
“These results are a setback for those affected by AD and for healthcare providers seeking new solutions. Despite careful selection of mild-to-moderate AD participants, cognitive decline in the placebo group was less severe than seen in other trials,” remarked Rick Barry, the chief executive officer. “The outcome impacts our second phase 3 trial, ReFocus-ALZ, leading us to the difficult decision to halt it based on today’s findings. Comprehensive 52-week data, alongside 76-week samples, will be released later with detailed studies of both trials. The Open Label Extension study will also be concluded.”
Barry added, “We extend sincere gratitude to participating patients, their relatives, and caregivers within our AD clinical program, as well as to our dedicated team, study practitioners, site coordinators, and other partners. We aim for the accumulated information to advance AD research.”
Below is a concise overview of the co-primary endpoint findings. The primary analysis of mild and moderate sub-groups similarly lacked statistical significance by week 52.
ReThink-ALZ (NCT04994483) represents a phase 3 investigation focused on simufilam’s safety and efficacy versus placebo in a broad, multi-center, double-blind, placebo-controlled, randomized parallel group framework across over 75 clinical sites in the US, Canada, and Australia. The trial involved 804 individuals diagnosed with mild or moderate AD, defined by specific criteria including a mini-mental state examination (MMSE) of >16 and <27, divided into mild or moderate. Participants were randomly assigned 1:1 to receive 100 mg simufilam (n=403) or placebo (n=401) twice daily (BID) over 52 weeks. Primary aims focused on shifts in cognition and function from start to week's end at the conclusion of the double-blind treatment, assessed via ADAS-COG12 and ADCS-ADL scales, comparing simufilam to placebo. Secondary objectives encompassed validated assessments of neuropsychiatric symptoms and caregiver strain. Safety underwent evaluation via various metrics, including adverse event tracking. The study incorporated a pharmacokinetics and plasma biomarker sub-study involving roughly 100 participants assessed at three intervals. Conducted under a Special Protocol Assessment (SPA) with the US FDA, ReThink-ALZ aims to further research in Alzheimer's disease. Simufilam, an exclusive investigational oral small molecule, targets filamin A protein. Operating out of Austin, Texas, Cassava Sciences is a clinical-stage biotechnology company committed to diagnosing and addressing neurodegenerative conditions like Alzheimer's disease.