The US Department of Justice (DOJ) has reportedly opened a criminal investigation into Cassava Sciences just 1 week after a neuroscientist alleged in an expose that the company's studies of the experimental Alzheimer's drug simufilam appeared to include altered images.
A Reuters news story reported that the DOJ had opened an investigation that would be overseen by DOJ staff who investigate fraud against investors, consumers, and the federal government. The DOJ did not return a request for comment by press time. The department does not generally comment on investigations.
In response to the Reuters report, Remi Barbier, president and CEO of Cassava, said in a statement that no charges have been filed against the company and that allegations of research misconduct are false.
"No government agency has informed us that it has found supporting evidence of research misconduct or any other wrongdoing and for good reason ― there is no supporting evidence for allegations of research misconduct," he said.
Based in Austin, Texas, Cassava has been surrounded by controversy almost since its start in 2019.
Most recently, Matthew Schrag, MD, PhD, an Alzheimer's researcher with Vanderbilt University Medical Center in Nashville, Tennessee, alleged in an expose in the journal Science that it appeared Cassava's research included altered or duplicated brain images that have appeared in dozens of journal articles supporting the efficacy of simufilam. Schrag filed a whistleblower report with the National Institutes of Health, which has spent millions funding the drug's development.
After the expose was published, Schrag told Medscape Medical News in an interview that "a lot is at stake in terms of getting this right, and it's also important to acknowledge the limitations of what we can do. We were working with what's published, what's publicly available, and I think that it raises quite a lot of red flags, but we've also not reviewed the original material because it's simply not available to us."
He added that despite these limitations, he believes "there's enough here that it's important for regulatory bodies to take a closer look at it to make sure that the data is right."
The Science feature article described how Schrag was hired in August 2021 by the law firm Labaton Sucharow to analyze Cassava studies for a citizen's petition the firm had filed with the US Food and Drug Administration (FDA).
Labaton Sucharow wanted the FDA to put a hold on Cassava's trials until alleged irregularities in the research could be investigated. The firm represented short sellers — investors who make money on a stock when its price falls.
Schrag received $18,000 for his analysis, but he told Science that he has never shorted Cassava stock. If anything comes of any whistleblower investigations ― including investigations by the DOJ ― Schrag could be eligible to receive a portion of whatever is recovered by the federal government.
In November 2021, the Wall Street Journal (WSJ) ran a news story about the petition and spoke to some of the short sellers behind the effort, including David Bredt, a neuroscientist, and Geoffrey Pitt, a cardiologist. The WSJ reported that the Securities and Exchange Commission had opened an investigation into claims that Cassava had manipulated study results.
Cassava said in its statement that in November, it publicly disclosed that "certain government agencies had asked for corporate information and documents." The company has "been cooperating with government authorities," and, it added, "no government agency has informed us that Cassava Sciences, or anyone associated with us, has engaged in any wrongdoing."
Cassava claims that short sellers ― who have made a reported $100 million ― are behind the attacks on the company.
"For a $100 million payday, some investors may be incentivized to make false allegations," said Barbier, who added, "Our goal is to help people with Alzheimer's disease, not an easy payday."
Science reported that after reviewing the Cassava studies, Schrag also flagged images in articles by Sylvain Lesné, PhD, who runs the Lesné Laboratory at the University of Minnesota, in Minneapolis, and is an associate professor of neuroscience.
Lesne's 2006 article in Nature, which identified an amyloid beta (Aβ) subtype as a potential culprit behind AD, is viewed as foundational and served as the basis of Cassava's research.
In an independent review of Schrag's findings undertaken by Science, several Alzheimer's researchers agreed with Schrag's overall conclusions that something was amiss.
Amyloid Hypothesis Not Dead
Among those experts was Donna M. Wilcock, PhD, assistant dean of biomedicine and associate director of the Sanders-Brown Center on Aging at the University of Kentucky College of Medicine.
Wilcock told Medscape Medical News that she found that "there were instances of cropping, editing, and duplicating of bands" in the Western blots in articles by Lesne and colleagues that she reviewed. If those instances are verified, "such manipulation is a blatant example of misconduct that spans multiple publications by the Lesné group," she said.
However, she added, any misconduct by Lesne or Cassava "does not negate the entire amyloid hypothesis."
Rudy Tanzi, PhD, who holds the Joseph P. and Rose F. Kennedy Professorship of Neurology at Harvard Medical School, agreed.
"While the apparent manipulation of data in that 2006 paper is unacceptable and egregious, that study has actually had very little influence on the amyloid hypothesis or the direction of Alzheimer research," he told Medscape Medical News.
"By 2008, we knew that the data in that  paper [by Lesné] could not be replicated in both published and unpublished studies," said Tanzi, who also s director of the Genetics and Aging Research Unit at Harvard.
Tanzi believes there is more promise in focusing on the naturally occurring smaller Aβ oligomers, which, he said, "have been shown to drive Alzheimer pathology decades in advance of symptoms."
Alicia Ault is a Lutherville, Maryland–based freelance journalist. You can find her on Twitter @aliciaault.
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Cite this: DOJ Reportedly Opens Criminal Inquiry Into Alzheimer's Drug Research - Medscape - Jul 29, 2022.