Cassava Sciences is facing renewed calls to halt its Phase 3 clinical trials for simufilam, an experimental drug for Alzheimer's disease, amid persistent allegations of data manipulation and scientific misconduct. The company recently resolved an SEC investigation by agreeing to pay $40 million over claims it misled investors with doctored data from a Phase 2 trial. These accusations, coupled with independent expert analyses questioning the drug's scientific basis, have intensified scrutiny on the ongoing trials.
SEC Settlement and Data Manipulation Claims
The SEC's charges stem from a Phase 2 trial of simufilam, where consultant Hoau-Yan Wang allegedly manipulated data to create the appearance of significant improvements in Alzheimer's biomarkers, such as total tau. The SEC alleges that Wang had access to unblinded data and that Cassava published these results without disclosing Wang's financial stake in the trial's success or the full patient data. The SEC also charged Cassava’s former CEO and senior vice president of neuroscience for their roles in publishing the data. While Cassava's new CEO, Richard Barry, aims to move forward, the settlement has not quelled concerns about the integrity of the company's research.
Independent Scrutiny and Scientific Concerns
Matthew Schrag, a vascular neurologist and assistant professor of neurology at Vanderbilt University, has been a vocal critic of Cassava's work. Schrag's analysis of Cassava's preclinical and early-stage data revealed "anomalies" in images and raised concerns about the drug's mechanism of action. He described simufilam as a "hodge-podge" mix of the beta-amyloid hypothesis and the idea of restoring acetylcholine levels, arguing that there is virtually no supportive evidence for this approach outside of Cassava. Schrag contends that the Phase 3 program is built on "tampered" data and that there is "no rationale" to continue the trials.
Regulatory and Ethical Considerations
The FDA previously denied a petition to halt Cassava's clinical program, but suspicions surrounding the company's work have persisted. An FDA investigation into a CUNY lab used by Wang revealed improper equipment maintenance and a lack of data security. Furthermore, Wang was indicted by the Department of Justice for allegedly defrauding the NIH out of $16 million in grant funding. Despite these issues, Cassava's clinical team continues its work, with a safety review board recommending that the Phase 3 trials proceed as planned.
Patient Advocacy and Scientific Integrity
While patient advocacy groups generally support the study of new treatments, Alzheimer's Association CEO Joanne Pike declined to comment on whether Cassava's trials should continue, citing a lack of access to all the data and information the FDA uses in its decisions. However, Pike emphasized the importance of a participant-centered approach to research and responsible communication with trial participants. She also stressed that "putting profits ahead of people" and "scientific misconduct" are unacceptable, and commended the SEC's investigation, urging federal agencies to aggressively pursue all credible allegations of misconduct.
Cassava expects top-line data from its first Phase 3 study by the end of this year and more results from the second trial by mid-2025. The outcome of these trials and the ongoing scrutiny will likely determine the future of simufilam and Cassava's role in the Alzheimer's treatment landscape.
