Simufilam Phase 3 Results Miss Co-Primary Endpoints

Cassava Sciences, Inc., a clinical-stage biotechnology company based in Austin, Texas, announced that the Phase 3 ReThink-ALZ study findings for their investigational Alzheimer’s disease (AD) treatment, simufilam, did not achieve the desired outcomes. Despite comprehensive efforts, the trial results did not meet the co-primary, secondary, and exploratory biomarker objectives.

Simufilam, developed as an oral small molecule drug targeting the filamin A protein, was evaluated in a randomized, double-blind study. The co-primary endpoints focused on changes in cognitive and functional abilities from the baseline to the 52-week mark, using the ADAS-COG12 and ADCS-ADL scales. The study compared the performance of simufilam against a placebo.

Rick Barry, the President and CEO of Cassava Sciences, expressed disappointment over the results. He noted that despite their meticulous approach to patient selection, cognitive decline in the placebo group was less severe than expected when compared to previous placebo-controlled Alzheimer's studies. This unexpected outcome is under further investigation.

The disappointing results have led Cassava Sciences to halt their second Phase 3 trial, ReFocus-ALZ. This trial had been designed to build on the findings of ReThink-ALZ. The company plans to analyze and report detailed data from both studies in the future. Additionally, Cassava will discontinue the Open Label Extension study associated with these trials.

Barry conveyed his gratitude to the patients, their families, and the caregivers involved in the clinical program. He also acknowledged the dedication of the company’s employees, study investigators, site coordinators, and other partners. The information gathered from these studies is hoped to contribute significantly to ongoing research in Alzheimer's disease.

The ReThink-ALZ study was a large-scale endeavor involving over 75 clinical trial sites across the U.S., Canada, and Australia. A total of 804 patients with mild-to-moderate Alzheimer's were randomized 1:1 to receive either simufilam or a placebo for 52 weeks. These participants were assessed based on a mini-mental state examination (MMSE) score that categorized them as either mild or moderate cases of AD. Secondary endpoints of the study included various neuropsychiatric and caregiver burden measures, while safety was monitored through multiple metrics including adverse event tracking.

Cassava Sciences’ mission centers on identifying and treating neurodegenerative diseases, particularly Alzheimer's. Their investigational drug, simufilam, has been a key focus, leveraging the company’s proprietary research and technology. Despite these recent setbacks, the company remains committed to contributing to the understanding and treatment of neurodegenerative conditions.

In summary, the Phase 3 trial for simufilam in treating Alzheimer’s disease did not achieve its predefined objectives, leading to the cessation of the ReFocus-ALZ trial and the Open Label Extension study. Cassava Sciences is dedicated to analyzing the complete data set and contributing to future Alzheimer’s research.