On November 25, Cassava Sciences announced that the Phase III ReThink-ALZ study of Simufilam for the treatment of mild to moderate Alzheimer's disease (AD) did not meet the pre-specified dual primary endpoints, secondary endpoints, and exploratory biomarker endpoints.

Compared with the placebo group, there was no obvious improvement trend in the ADAS-COG12 and ADCS-ADL scale scores of patients in the trial group. Among them, the test results obtained by the ADCS-ADL scale showed that the situation in the trial group was even worse than that in the placebo group. After the news of the failure of the Phase III study leaked, Cassava's stock price plummeted 85% to US$3.91, while the previous closing price was US$26.48.
Since the beginning of 2021, Simufilam's ability to reduce the toxic effects of β-amyloid protein has been questioned.

Two neuroscientists, Geoffrey Pitt and David Bredt, filed a petition with the U.S. Food and Drug Administration (FDA) to suspend clinical trials of Simufilam, citing signs of image manipulation in multiple papers of the study that undermine the claim that Simufilam can slow or even reverse symptoms of Alzheimer's disease.

The National Institutes of Health (NIH) asked the City University of New York (CUNY) to review the researchers' papers, conference posters, and NIH grant applications published between 2003 and 2021, and completed a 50-page report in May 2023, accusing the drug's main developers of academic misconduct in 20 research papers, including image manipulation. CUNY's investigation report ultimately concluded that the researcher had "long-term and serious academic misconduct in data management and record keeping."

In 2022, FDA investigators found that the researcher had serious problems in handling abnormal data. After a deeper investigation, it was found that he had never routinely calibrated the equipment and had not completed validation experiments to ensure the accuracy, sensitivity and precision of the test. Inappropriate statistical tests were also used, resulting in inaccurate sample concentration measurements.

After a series of investigations, the researcher was indicted by the U.S. Department of Justice (DOJ) in June 2023 for "defrauding the National Institutes of Health (NIH) of approximately $16 million in grants." If convicted, the researcher faces up to 10 years in prison.