Cassava Sciences has revealed the late-stage clinical failure of controversial Alzheimer’s drug simulfilam. The company had pledged to share the results whether “good, bad or ambiguous.”
After promising to set the record straight on the potential of simufilam to help with Alzheimer’s disease, Cassava Sciences reported Monday that the drug has failed in a much-anticipated Phase III trial.
Simufilam did not reduce cognitive or functional decline when compared with placebo in patients with mild-to-moderate Alzheimer’s disease in the trial called ReThink-ALZ, Cassava said in its press release. The trial failed on all pre-specified co-primary, secondary and exploratory biomarker endpoints. The main outcome measured change in cognition and function at week 52 compared to baseline. The other goals included improvements in neuropsychiatric symptoms and caregiver burden.
CEO Rick Barry said in the announcement that the company “took careful measures” to pick patients with mild-to-moderate disease, but the placebo group showed “less pronounced” cognitive decline than expected based on previous Alzheimer’s trials. Cassava is “working to understand this better,” Barry said.
In the meantime, Cassava is ending a second Phase III trial called ReFocus-ALZ, which evaluated a different dose of simufilam, as well as an expanded access program.
Cassava’s shares plunged 85% to $3.91 as the markets opened Monday morning, compared to $26.48 at the previous close.
The clinical failure caps a tumultuous few years for Cassava. In began in August 2021, when a whistleblower urged the FDA to step in and stop clinical trials for simufilam citing signs of data manipulation in some of Cassava’s results. An investigation into the allegations by the City University of New York revealed evidence last year that “highly” suggested “deliberate misconduct” by an advisor to Cassava, and the company recently settled an SEC lawsuit alleging data manipulation in earlier studies for simufilam for a $40 million fine.
Cassava had presented simufilam as a new approach to Alzheimer’s. The oral drug targets the scaffolding protein filamin A in the brain with the aim of restoring its normal shape and function. Simulfilam is Cassava’s lead, and apparently only, drug in development.
Barry took the helm in September after longtime CEO Remi Barbier left earlier this year. During a third quarter earnings report, Barry promised to report the Phase III results “whether it is good, bad or ambiguous.” The pledge was a turnaround from previous readouts from the company, which were muddled with post-hoc analyses in an apparent attempt to turn unsuccessful data into something positive.
This time around, Cassava was straightforward, announcing in the headline of the release that the trial was unsuccessful. The company held a conference call but did not take questions. The call kept to prepared remarks and strayed little from the press release.
“We said that we would be forthcoming with our data and release it whether it was good, bad or indifferent. We are living up to that commitment today, although this is by no means the news we were hoping for,” Barry said on the call.
Beyond the end of the second Phase III trial, Cassava was mum on what happens next. CFO Eric Schoen said: “We remain focused on the interests of Cassava shareholders and are committed to enhancing shareholder value. Cassava is well-capitalized with approximately $149 million in cash and cash equivalents as of the end of the third quarter of 2024.”
Data from the ReThink-ALZ trial will be shared at a future medical meeting.
