Cassava Sciences' experimental drug, simufilam, for Alzheimer's disease has failed to meet its primary endpoints in the Phase 3 ReThink-ALZ study, leading to the termination of its clinical program. The trial, designed to assess the drug's efficacy in patients with mild-to-moderate Alzheimer's, did not demonstrate a significant change in cognition and function compared to placebo after 52 weeks of treatment.
The co-primary endpoints of the study were the change in cognition and function from baseline to week 52, as measured by the ADAS-COG12 and ADCS-ADL scales. Despite enrolling patients with mild-to-moderate Alzheimer's, the placebo group showed a less pronounced cognitive decline than anticipated, according to Cassava Sciences CEO Rick Barry. Simufilam did demonstrate a favorable safety profile.
Impact on Clinical Development
Following the negative results from the ReThink-ALZ study, Cassava Sciences has decided to discontinue its second Phase 3 trial, ReFocus-ALZ, as well as the Open Label Extension study. This decision marks the end of the clinical development program for simufilam, a drug that had been the subject of considerable controversy.
Background of Controversy
Cassava Sciences has faced scrutiny over allegations of data manipulation in simufilam's clinical trials. In September, the company agreed to pay over $40 million to settle charges with the SEC related to misleading statements made about a Phase 2 trial. The SEC also charged Hoau-Yan Wang, a consultant and co-developer of the drug, with manipulating trial results. The investigation revealed that Cassava disclosed manipulated data in September 2020, falsely suggesting significant improvements in Alzheimer's biomarkers.
Future Steps
Cassava Sciences plans to share the detailed results from the ReThink-ALZ study at a future medical meeting. The company will continue to review the data to determine its next steps. The complete 52-week dataset, along with a portion of the 76-week data, will be made available for further analysis.
