The biopharma company Cassava Sciences announced today its experimental Alzheimer’s disease drug simufilam showed no signs of working in a phase 3 clinical trial. Volunteers who took the drug performed no better in cognitive or everyday-life activities than those who received a placebo. The announcement appears to mark the end of the company’s development of simufilam for Alzheimer’s, which has been marked by scandal and controversy.
Simufilam, which was supposed to counteract protein changes driving Alzheimer’s, failed to meet any primary, secondary, or exploratory end points, the company said. Besides failing to reduce symptoms, it showed no signs of beneficial effects on biomarkers associated with Alzheimer’s—although it showed no serious adverse effects. The company says it has halted a separate phase 3 trial whose results were due next year. The two studies included nearly 2000 volunteers. Cassava also ended the open-label extension phase of an earlier trial—in which participants and doctors knew the drug was given, rather than a placebo.
Simufilam’s problems began in 2021, when a law firm representing two whistleblowers, who stood to profit if Cassava’s stock fell, filed a citizen’s petition with the U.S. Food and Drug Administration (FDA). It alleged that basic research studies that had been used to justify moving ahead with clinical trials of the drug included fraudulent images.
Science reported last year that City University of New York neuroscientist Hoau-Yan Wang—co-discoverer of the experimental compound—was found by a university panel to have engaged in “egregious misconduct” associated with his work for Cassava. Earlier this year, Science revealed FDA had found major lapses in Wang’s laboratory procedures for testing clinical samples for a simufilam study. Wang was indicted by the U.S. Department of Justice in June for “defrauding the National Institutes of Health of approximately $16 million” in grants related to simufilam and Cassava.
Then in September the company agreed to pay $40 million to the Securities and Exchange Commission (SEC) to settle charges that it had misled investors about earlier clinical trial results for simufilam. It had claimed a phase 2 trial showed dramatic improvements in Alzheimer’s patients. Cassava’s original CEO, Remi Barbier, and one of the company’s chief scientists, Lindsay Burns, left the company, paid fines as part of their own SEC settlements, and were barred by SEC from serving as officers or directors of a public company for several years. Wang also paid a fine to settle related charges.
“This is an expected result,” says Matthew Schrag, a Vanderbilt University neuroscientist who discovered many of the apparently doctored images cited in the complaint to FDA. “It remains alarming to me that the trial was permitted to continue to completion in view of the serious ethical concerns around the underlying science.” Schrag, who has conducted his assessments of Cassava’s work separately from his university duties, provided much of the basis for the citizen’s petition to FDA and has tracked the company since.
Elisabeth Bik, a leading forensic image sleuth, also identified many of the problems in Cassava’s studies—and was relentlessly attacked by boosters of the company on social media. The self-described “SAVAges,” a play on the company stock-ticker symbol, had for years lambasted Bik and other Cassava critics, including journalists who wrote about the company, in often-caustic and at-times threatening terms.
The company has only one drug in development, making its future uncertain at best. Its stock plummeted by more than 80% on the news—dropping about $1 billion in value.
“This is by no means the news we were hoping for,” Rick Barry, the company’s CEO, said in a conference call.
