Cassava Sciences' Phase 3 ReThink-ALZ study evaluating simufilam for mild-to-moderate Alzheimer's disease (AD) did not meet its pre-specified co-primary endpoints, leading to the discontinuation of the simufilam program. The trial, which involved 804 patients, aimed to assess the change in cognition and function using the Alzheimer's Disease Assessment Scale-Cognitive Subscale 12 (ADAS-COG12) and the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale at week 52.
Detailed Results of ReThink-ALZ
The ReThink-ALZ study was a multi-center, double-blind, placebo-controlled, randomized trial conducted across more than 75 sites in the U.S., Canada, and Australia. Participants with confirmed mild or moderate AD were randomized 1:1 to receive either simufilam 100 mg or a matching placebo twice daily for 52 weeks. The co-primary endpoints focused on changes from baseline to week 52 in cognition and function. Secondary endpoints included measures of neuropsychiatric symptoms and caregiver burden. The study also incorporated a pharmacokinetic and plasma biomarker sub-study.
Topline data revealed no statistically significant difference between the simufilam and placebo groups in either ADAS-COG12 (simufilam: 2.8, placebo: 3.2, p=0.43) or ADCS-ADL (simufilam: -3.3, placebo: -3.8, p=0.40). Subgroup analyses of mild and moderate AD patients also failed to demonstrate statistical significance.
Safety and Tolerability
Simufilam demonstrated an overall favorable safety profile. The most frequent adverse events (AEs) in the simufilam group were COVID-19 (8.0%), urinary tract infection (7.8%), fall (7.5%), dizziness (5.3%), and headache (4.5%). Serious AEs occurred in 13.0% of patients in the simufilam group and 9.0% in the placebo group. Discontinuation due to AEs was slightly higher in the simufilam group (6.5%) compared to placebo (4.3%).
Discontinuation of Further Studies
Following the disappointing results, Cassava Sciences has decided to discontinue its second Phase 3 trial, ReFocus-ALZ, and the open-label extension study. "The results are disappointing for patients and their families who are living with this disease and physicians who have been looking for novel treatment options," said Rick Barry, President and CEO of Cassava Sciences. "A result like this has implications on our second Phase 3 trial, ReFocus-ALZ. We have made the difficult decision to discontinue ReFocus-ALZ, given the nature of today’s reported results."
Future Plans
Cassava Sciences plans to present detailed analyses of both the ReThink-ALZ and ReFocus-ALZ studies at a future medical meeting. The company remains focused on enhancing shareholder value and has approximately $149.0 million in cash and cash equivalents as of the end of the third quarter of 2024.
