Cassava Sciences' experimental Alzheimer's drug, simufilam, has failed to meet its primary endpoints in a Phase III clinical trial, leading to a significant drop in the company's stock price and the termination of its development program. The trial, named ReThink-ALZ (NCT04994483), enrolled over 1,900 patients with mild to moderate Alzheimer's disease but did not demonstrate a significant reduction in cognitive or functional decline compared to placebo after 52 weeks.
The co-primary endpoints of the trial were the change in cognition and function after one year, as assessed by the Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAS-COG12) and the Alzheimer's Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scales. The study also failed to meet secondary and exploratory biomarker endpoints.
Disappointing Results and Future Implications
"The results are disappointing for patients and their families who are living with this disease and physicians who have been looking for novel treatment options," said Cassava Sciences CEO Rick Barry in a statement. He noted that the loss of cognition in the placebo group was less pronounced than previously reported in other placebo-controlled studies in Alzheimer's disease, a factor the company is working to understand.
As a result of the negative data, Cassava Sciences has decided to discontinue its second Phase III trial, ReFocus-ALZ (NCT05026177), which was evaluating a different dose of simufilam, as well as an open-label extension study (NCT05575076). This decision effectively ends all development of simufilam, which was the company's only drug in clinical trials, placing Cassava's future in flux.
Stock Plunge and Financial Impact
Following the announcement, Cassava Sciences' stock price plummeted by over 80%, from a market close of $26.48 on Friday, November 22, to an opening of $3.96 on Monday, November 25. This represents a significant blow to the company's investors, who once valued Cassava at over $5 billion.
Background and Controversy
Simufilam's development has been plagued by controversy. Studies that initially seemed to support the drug have been retracted from scientific journals, and a consultant researcher who helped conduct some of the drug's foundational studies was charged with fraud for allegedly falsifying data to obtain research grants. In September, Cassava settled with the Securities and Exchange Commission (SEC) over allegations that it made misleading statements about earlier clinical trial data, though the company neither admitted nor denied wrongdoing.
Despite these issues, Cassava continued to advance simufilam through clinical trials, maintaining that there was still research and clinical results suggesting the drug could prove valuable. However, the Phase III results have dashed these hopes.
Simufilam's Mechanism of Action
Cassava had presented simufilam as a novel approach to treating Alzheimer's disease. The oral drug was designed to target the scaffolding protein filamin A in the brain, with the aim of restoring its normal shape and function. However, the Phase III trial results indicate that the drug failed to achieve its intended effect.
Company's Response
Cassava Sciences has stated that it will present the negative trial data and make it available to other researchers. The company remains focused on the interests of its shareholders and is committed to enhancing shareholder value. As of the end of the third quarter of 2024, Cassava had approximately $149 million in cash and cash equivalents.
