Cassava Sciences has officially stopped the development of its investigational drug simufilam in Alzheimer’s disease after it failed to show benefit in a second Phase III trial.
The company is now pursuing development in other central nervous system disorders.
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The US biotech reported that its candidate simufilam failed to meet prespecified co-primary, secondary and exploratory biomarker endpoints in the REFOCUS-ALZ trial (NCT05026177). The co-primary endpoints were the change in cognition and function from baseline to the end of the double-blind treatment period at week 76, assessed by the ADAS-COG12 and ADCS-ADL scales.
REFOCUS-ALZ enrolled 1,125 patients and was discontinued on 25 November 2024 after the company reported that the Phase III RETHINK-ALZ trial (NCT04994483) also failed to meet its co-primary endpoints.
Cassava conceded that simufilam demonstrated an overall favourable safety profile.
Cassava president Rick Barry said: “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.
“Cassava will discontinue all efforts to develop simufilam for Alzheimer’s disease and we expect to phase out the program by the end of Q2 2025.”
In November 2024, the company’s stock, listed on the Nasdaq exchange, crashed by 85% after the RETHINK-ALZ trial data was announced. On the 25 March update, Cassava’s stock dropped by 32%. In total, comparing the current stock price to its value just before the first failure announcement, the company has been hit with a 92.82% reduction.
Cassava chief financial officer Eric Schoen said: “We remain focused on the interests of Cassava shareholders and are committed to enhancing shareholder value. Cassava is well-capitalised with approximately $128.6m in cash and cash equivalents as of 31 December 2024.”
Cassava executives went on to say they are beginning investigations of simufilam in other central nervous system indications.
“While we have initiated preclinical studies to evaluate simufilam’s potential as a treatment for TSC-related epilepsy, we maintain ongoing strategic expense management efforts,” Barry concluded.
Previous controversy surrounding Cassava
Last year, Cassava Sciences had to pay $40m to settle a US Securities and Exchange Commission (SEC) case alleging misleading data from its Phase IIb trial of simufilam. The SEC’s case was set out against the Texas-based company and two former executives, founder and former CEO, Remi Barbier; and the former neuroscience senior vice president Dr Lindsay Burns.
A separate SEC case was set out against Dr Hoau-Yan Wang, an associate medical professor at the City University of New York’s (CUNY) Medical School and the therapeutic’s co-developer, for manipulating the reported clinical trial results. The SEC alleges that Wang violated antifraud provisions of the federal securities laws and that he aided and abetted Cassava’s violations of the reporting provisions.
The SEC charges are not the only difficulties faced by Cassava Sciences during its investigation of simufilam, having also launched a defamation lawsuit against ‘short sellers’ and faced a citizen petition to the US Food and Drugs Administration (FDA) to halt clinical trials of the drug.
