Cassava Sciences Ends Alzheimer's Program as Simufilam Fails in Phase III Trials

Cassava Sciences has officially discontinued its Alzheimer's disease program for the drug simufilam, marking the end of a tumultuous journey plagued by controversy and clinical trial failures. The decision comes after the release of disappointing topline results from two Phase III trials, REFOCUS-ALZ and RETHINK-ALZ, which showed no significant treatment benefit for patients with mild to moderate Alzheimer's disease.

Failed Clinical Trials and Program Discontinuation

The REFOCUS-ALZ trial, results of which were announced on March 25, 2025, demonstrated that simufilam did not reduce cognitive or functional decline compared to placebo in patients with mild to moderate Alzheimer's disease. The drug failed to meet its prespecified co-primary, secondary, and exploratory biomarker endpoints.

Specifically, on the ADAS-COG12 scale, where lower scores indicate less cognitive impairment, patients in the simufilam cohorts showed an increase of 4.97 and 5.26 points, while the placebo group increased by 4.70 points. Similarly, on the ADCS-ADL scale, where higher scores signify less functional impairment, simufilam-treated patients experienced declines of 6.27 and 6.43 points, compared to a 5.32-point decline in the placebo group.

These results follow the earlier failure of the RETHINK-ALZ trial, reported in November 2024, which also showed no effect on cognitive and functional decline in Alzheimer's patients.

Cassava Sciences CEO Rick Barry stated, "We are disappointed that the results of REFOCUS-ALZ and RETHINK-ALZ showed no treatment benefit for patients with mild-to-moderate Alzheimer's disease. These results were unambiguous." The company plans to phase out the Alzheimer's program entirely by the end of the second quarter of 2025.

Company History and Controversies

Cassava Sciences' journey with simufilam has been marked by significant challenges and controversies. In 2021, the company faced allegations of data manipulation, leading to the retraction of some research papers related to the drug. These claims prompted investigations by both the Securities and Exchange Commission (SEC) and the Department of Justice (DOJ).

The controversy resulted in the departure of former CEO Remi Barbier in July 2024. Subsequently, the SEC filed a lawsuit against Cassava for publishing misleading data on simufilam.

Despite these setbacks, Cassava had maintained support from dedicated shareholders and some members of the scientific community. The company had previously touted simufilam as a potential breakthrough in Alzheimer's treatment.

Future Directions and Financial Position

While Cassava Sciences is discontinuing its Alzheimer's program, the company has begun exploring alternative applications for simufilam. In February 2025, Cassava licensed the rights to study the drug for seizures in neurodevelopmental disorders. The company has initiated preclinical studies to assess simufilam as a potential treatment for tuberous sclerosis complex (TSC)-related epilepsy.

However, CEO Rick Barry indicated that the company would maintain "ongoing strategic expense management efforts" as it pursues these new directions. Cassava Sciences reported a cash position of approximately $128.6 million in cash and cash equivalents as of December 31, 2024, which CFO Eric Schoen described as "well-capitalized."

The news of simufilam's failure and the discontinuation of the Alzheimer's program has had a significant impact on Cassava Sciences' stock price, with shares falling more than 20% following the announcement.