Cassava Sciences is advancing simufilam, its investigational drug for Alzheimer's disease, through a pivotal Phase 3 trial, even as the company addresses lingering controversy stemming from a Securities and Exchange Commission (SEC) investigation. With the trial's topline results anticipated before the end of the year, questions persist regarding the integrity of past data, despite efforts by new leadership to move forward.
The SEC previously charged Cassava and several former executives with making misleading statements related to Phase 2 clinical trial data. The SEC alleged that a Cassava-affiliated scientist, Hoau-Yan Wang, manipulated clinical trial results to create the appearance of significant improvements in biomarkers associated with Alzheimer's disease, such as total tau and phosphorylated tau. Cassava then released the altered data in a press release and investor deck, which led the SEC to allege that the company and its former CEO, Remi Barbier, misled investors.
The SEC's investigation revealed that Cassava allegedly failed to disclose that the full set of patient data from the Phase 2 trial showed no measurable cognitive improvement in the patients' episodic memory, despite the company claiming that there were significant improvements made by patients. As a result, Cassava was fined $40 million, while Barbier and the company's former SVP of neuroscience, Lindsay Burns, received civil penalties of $175,000 and $85,000, respectively. Wang consented to cease and desist from future violations and to pay a $50,000 penalty.
Cassava has since implemented remedial measures, including the departure of Barbier and Burns. Richard Barry has been appointed as executive chairman and temporary CEO. Barry emphasized the company's commitment to transparency, accountability, and ethical business practices. He also detailed the rigorous design and execution of the Phase 3 trial for simufilam, including the management of trial results by Premier Research International as the clinical research organization.
According to Barry, Premier Research International will complete its final review procedures regarding the completeness and accuracy of the data, and the database will be locked. No changes to the data will be made after database lock. The company's stock price experienced a significant drop following the SEC investigation results but has since recovered. The upcoming Phase 3 results are critical for the company, as simufilam is its only asset in development. Any regulatory filing will likely be reviewed with additional scrutiny, given the highly public case and questions over the integrity of Phase 2 data.
Simufilam's Potential Impact
Simufilam is being developed as a treatment to slow the progression of Alzheimer's disease, a condition affecting millions worldwide. Current treatments, such as Leqembi (lecanemab) from Eisai and Biogen, and Kisunla (donanemab) from Eli Lilly, have shown some efficacy in reducing cognitive decline, but have also faced challenges and controversies. The approval of these new therapies has not been without difficulty and some controversy. Leqembi was rejected by an EU panel based on safety data, while Biogen pulled its previous Alzheimer’s treatment from the market entirely based on a lack of uptake.
Trial Design and Endpoints
The Phase 3 trial of simufilam is designed to evaluate its efficacy and safety in patients with Alzheimer's disease. The trial's primary endpoints likely include measures of cognitive and functional decline, while secondary endpoints may assess changes in biomarkers and other clinical outcomes. The dosing regimen and administration route for simufilam are critical aspects of the trial design. The patient population and inclusion criteria are also important factors in determining the applicability of the trial results.
Regulatory Scrutiny Ahead
Given the past data integrity issues, any regulatory filing for simufilam will likely face intense scrutiny from the FDA and other regulatory bodies. A citizen's petition had previously called for the FDA to halt clinical trials of simufilam, but the agency declined, stating that the calls for it to instigate an investigation and make public disclosures are outside of its remit. The FDA and other regulatory bodies are likely to tread very carefully when reviewing Cassava’s potential regulatory filing.
