Cassava Sciences revealed that the topline results from the phase 3 ReThink-ALZ study of its controversial Alzheimer’s drug, simufilam, did not meet any of the pre-specified co-primary, secondary or exploratory biomarker endpoints.
In the trial, which involved 804 people with confirmed mild or moderate Alzheimer’s, simufilam failed to best placebo in both primary endpoints — change in cognition and change in function from baseline to the end of the double-blind treatment period at week 52, assessed by the ADAS-COG12 and ADCS-ADL scales.
Secondary endpoints included several well validated measures of neuropsychiatric symptoms and caregiver burden. The study also included a pharmacokinetic and plasma biomarker sub-study comprised of approximately 100 subjects, evaluated at three timepoints.
Given the results of the ReThink-ALZ study, the Texas-based biotech says it will also discontinue its second phase 3 trial, ReFocus-ALZ.
Simufilam, an oral, small molecule drug, takes a new approach to Alzheimer’s by aiming to restore the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. But the trial failure likely marks the end of a drug that has been plagued with controversy for years.
Back in 2021, two whistleblowers claimed Cassava’s simufilam research was “riddled with red flags,” sending a citizen's petition to the FDA requesting that the agency halt two ongoing trials of the drug. In November 2021, the Wall Street Journal reported that the SEC had launched an investigation into the manipulated data. In July 2022, the DOJ launched a criminal probe into the possibility of manipulated research.
In June 2024 the DOJ indicted a scientist who had been involved in the clinical trial for simufilam for defrauding the National Institutes of Health of approximately $16 million in grants, accusing the scientist of fabricating results of his research submitted to NIH. This past September, Cassava, along with its former CEO and former senior VP of neuroscience, agreed to will pay more than $40 million to settle the SEC charges related to misleading statements made in September 2020 about the results of a phase 2 clinical trial for simufilam.
Throughout all of this, Cassava has maintained its innocent of wrongdoing, and insisted in the integrity of its simufilam data.