Regulatory officials and Alzheimer's researchers are raising concerns about the efficacy and data integrity surrounding Cassava Sciences' investigational drug, simufilam, for Alzheimer's disease. This scrutiny follows a $40 million settlement with the Securities and Exchange Commission (SEC) over allegations of data manipulation and misleading claims regarding the drug's effectiveness.
Despite these serious allegations, Cassava Sciences is proceeding with its Phase 3 clinical trials, which have enrolled over 1,900 patients diagnosed with mild to moderate Alzheimer's disease. The company maintains that its remaining research and clinical results suggest simufilam may still offer potential benefits for patients.
Ethical Questions Surround Ongoing Trials
However, experts in the field are questioning the ethics of continuing the trials given the unresolved concerns about data integrity. George Perry, an Alzheimer's researcher from the University of Texas at San Antonio, expressed his bafflement, stating, "If the efficacy and the underlying data is being questioned, which it is, why would you continue the study?"
Matthew Schrag, a neurologist and assistant professor at Vanderbilt University, echoed these concerns, stating that continuing the trials is "unethical" given the serious concerns surrounding the underlying data. "When we violate our ethical responsibilities to these patients, we're undermining the future of clinical trials in this space," Schrag said.
Allegations of Data Manipulation
The SEC's charges against Cassava Sciences' former CEO Remi Barbier and former VP Lindsay Burns allege that they made misleading statements about Phase 2 clinical trials for simufilam. The SEC order claims that Burns selectively presented data to create the impression that participants on the drug experienced memory improvement, when the overall trial results were actually negative.
Hoau-Yan Wang, the drug's co-developer and former paid advisor, also faces charges from the SEC for allegedly manipulating clinical trial results. Wang is accused of receiving unblinded data and falsifying the data to suggest that simufilam reduced Alzheimer's biomarkers.
FDA's Role and Previous Scrutiny
In 2021, a citizen petition was filed with the FDA urging the agency to halt clinical trials of simufilam, citing allegations of fraudulent research. While the FDA denied the petition, independent experts have continued to raise concerns about anomalies in the company's data, leading to multiple investigations.
The FDA has the authority to pause or terminate clinical trials if it identifies issues related to data integrity. While the agency has not commented specifically on the simufilam situation, it routinely reviews trials and takes actions to protect participants.
Uncertain Future for Simufilam
Cassava Sciences is currently conducting two Phase 3 trials of simufilam, with results expected by the end of the year. However, the ongoing controversies surrounding the drug and the questions about data integrity cast a shadow over the trials' potential outcomes.
"If the studies were to, by some chance, have a positive outcome, nobody in their right mind could trust the outcome," Schrag said. He added that while Cassava Sciences' press releases indicate the drug is safe, he is uncertain whether the data can be trusted.
Given the ethical concerns and the potential risks to patients, Schrag believes that "any responsible regulatory agency involved in this process should be looking to take steps to protect these patients immediately."
