In June 2024, the United States Department of Justice charged an advisor to Cassava Sciences, Hoau-Yan Wang, with fraud over research results related to the experimental drug.
[8] Remi Barbier was Cassava's president, chief executive officer and chairman of the board[2][9] until his abrupt July 2024 resignation, when Richard J.
[9] Lindsay Burns the senior vice president for neuroscience and Barbier's wife[14][15][16][17] also resigned in 2024 following the indictment of her co-researcher Wang on charges of fraud.
[2] Keefe noted that part of the increase in share price was driven by discussion and hype in online forums, making it a so-called meme stock.
[19][26] Following the November 2024 announcement that simufilam had failed Phase III trials, Cassava stock fell to $4.29 per share, losing 84% of its value in one day.
[2][8] A 2022 article in The New York Times stated that none of the Alzheimer's experts they spoke with knew of any support for the FLNA hypothesis; Lawrence Sterling Honig, professor of neurology at Columbia University Irving Medical Center, said: "But in fact, all the evidence seems to be from this [Wang's] lab.
[33] Oxytrex was a mixture of two generic drugs, oxycodone and naltrexone that aimed to enhance analgesia while reducing opioid tolerance and withdrawal symptoms.
[35] In August 2020, the chemical name simufilam was assigned to the company's experimental drug, previously called PTI-125,[36] which Cassava Sciences says can restore misshaped FLNA in the brain.
[8] Open-label studies had started in March 2020,[8] and Cassava Sciences had reported in May 2020 that initial biomarker analysis of cerebrospinal fluid (CSF) samples from its phase IIb clinical trials of PTI-125 had failed, but reported in September 2020 that a new analysis by an "outside lab" showed improvements in biomarkers, adding that individuals with Alzheimer's also showed improvements in cognition with simufilam.
[39] In June 2024, Wang was indicted by the United States Department of Justice (DOJ)[40] for fraud and charged with falsifying data on $16 million in grant applications to the NIH related to simufilam.
[44] The charges filed in the United States District Court for the Western District of Texas alleged that Cassava violated "antifraud provisions of the federal securities laws" and "reporting provisions of the federal securities laws" and the SEC stated in a press release that "without admitting or denying the allegations, Cassava, Barbier, and Burns ... agreed to pay civil penalties of $40 million, $175,000, and $85,000, respectively.
[47] According to Science journal's Piller, "CUNY itself found Wang had committed 'egregious' scientific misconduct" and the SEC "charged that Wang had been 'unblinded' for patient fluid samples [while Burns] 'negligently failed to fully disclose' that she had removed data from 40% of the volunteers in a phase 2 simufilam clinical trial after learning which ones received simufilam or the placebo.
"[47] Piller wrote that the SEC complaint stated that Cassava had "raised more than $260 million from investors after that [phase 2] announcement", when in fact, "the complete data showed the drug failed to improve 'episodic' memory in Alzheimer's patients".
[15][22][48] The petition was submitted by Jordan A. Thomas, who was then with the law firm Labaton Sucharow in New York City, and requested that the FDA halt the clinical trials until the issues could be resolved.
[50] The petitioners who filed the FDA complaint were identified months later, in November 2021, as neuroscientist David S. Bredt,[2] and cardiologist Geoffrey Pitt, a professor at Weill Cornell Medical College.
[2][15] When the petition was filed, Bredt was an executive partner at a firm that raised investment capital for another biotechnology company working on Alzheimer's treatment.
[54] In July 2022, Science journal's Piller identified Vanderbilt University neuroscientist Matthew Schrag as another whistleblower who examined images.
Cassava refiled its suit against the four short-sellers in April 2024, but dropped the lawsuit in August after Wang was charged with submitting false data to the NIH.
[2] In October 2023, CUNY reported that they could obtain none of Wang's original data, which meant that they were unable to either prove or disprove allegations that the images were improperly manipulated;[60][61][62] they paused the investigation a few weeks later over concerns about confidentiality and integrity of the process.
[8] Robert Howard, professor of psychiatry at the University College London, remarked that the lack of placebo and small sample size meant research conclusions were "implausible" at the least.
[8] Elisabeth Bik, image-manipulation consultant, agreed to the citizen petition and alleged data errors and inconsistencies in the publications, identifying potential irregularities consistent with instances of copy and paste across different experiments.
[2] Thomas C. Südhof, Nobel laureate neuroscientist at Stanford University, also commented: "The overall conclusions with regard to Alzheimer's disease make no sense to me whatsoever... [The findings of Cassava Sciences] are not in the mainstream of the field, and to me they seem implausible and contrived.
[68] The journal Neurobiology of Aging found "no compelling evidence of data manipulation intended to misrepresent the results", but issued an expression of concern on a 2017 paper,[69] saying they identified multiple errors.
The FLNA retraction notices mention "vertical irregularities suggestive of splice lines" and that the "pixel patterns in background areas of blot images ... appear more similar than would be expected".
[22][75] He writes that the paper relied on a method of analyzing how brain tissue "purportedly generates chemical signals"; Schrag found no indication the work, which he says "contradicts basic neurobiology", had been replicated.