An upcoming Alzheimer’s drug that garnered millions in federal funding has officially been put to bed.
Biopharmaceutical company Cassava Sciences announced on November 25 that it had discontinued its Phase 3 clinical trial of drug simufilam. The randomized, double-blind trial found no statistically significant change in patient cognition or function—its co-primary endpoints—after 52 weeks when comparing a 403-person experimental group to a 401-placebo group of people with mild to moderate Alzheimer’s.
“The results are disappointing for patients and their families who are living with this disease and physicians who’ve been looking for novel treatment options,” Cassava President and CEO Rick Barry said in a webcast following the announcement.
This was the yearslong conclusion of a gradual fall from grace for a drug built on research that allegedly contained falsified data.
The Austin, Texas-based company’s stock dropped (alongside hopes for the drug) from $26.65 a share when markets closed November 22—prior to the results—to $4.02 when they reopened on November 25.
As of December 9, the stock price decreased even further to $3.18 a share when markets opened.
Back up—what happened?
Simufilam was a new approach to treating Alzheimer’s, attempting to alleviate symptoms by stabilizing a protein in the brain called filamin A that studies had linked with Alzheimer’s, according to Cassava Sciences’s website.
But other scientists were not convinced it could work.
Targeting filamin A is an approach to Alzheimer’s that is “not in the mainstream of the field,” Thomas Südhof, a Nobel laureate and neuroscientist at Stanford, told the New York Times in a 2022 article that questioned the science behind the drug.
“The overall conclusions with regard to Alzheimer’s disease make no sense to me whatsoever,” he told the New York Times.
An August 2021 citizen petition to the FDA also expressed “grave concerns about the quality and integrity of the laboratory-based studies surrounding this drug candidate.”
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The petition said that as of that time, all the evidence backing simufilam’s supposed treatment mechanism came from papers with two common Cassava-affiliated coauthors: Hoau-Yan Wang, a Cassava scientific collaborator and paid science advisor, and Lindsay Burns, Cassava’s former SVP of neuroscience.
In June 2024, a federal grand jury ruled that Wang had allegedly “manipulated or otherwise fabricated research results” about simufilam’s effectiveness.
On September 26, the US Securities and Exchange Commission (SEC) announced it had charged Cassava Sciences and several of its executives with making “misleading statements” and charged Wang with “manipulating” data.
Cassava Sciences, its founder and former CEO Remi Barbier, and Burns settled for $40+ million. Phase 3 trial data was analyzed by independent third-party firms, according to a form 8-K filing. But the trial’s end, nonetheless, was a final nail in the coffin for the drug.
Zooming out
Nicole Leclerc, a professor in the department of neuroscience at the University of Montreal, told Healthcare Brew in an email that she doubts filamin A will be researched as a drug target in Alzheimer’s research moving forward, as it would be difficult to target precisely.
Leclerc, who has coauthored research on filamin A and Alzheimer’s, said it’s “a very big protein that interacts with a lot of other proteins, and therefore directly targeting it could have several side effects.”
She believes this controversy is a symptom of a larger problem in her field.
“Several cases of falsified data were reported in the field of Alzheimer’s research. Because of all the money that was invested (several billions) and the numerous failures in clinical trials, there is a lot of pressure to find a cure. This pressure favors frauds,” she said.