A law firm known for filing shareholder suits says that data supporting a drug company’s plan for trials of its experimental treatment for Alzheimer’s disease show evidence of manipulation.
Stock in the company, Cassava Biosciences, tumbled yesterday after the FDA posted material from the firm, Labaton Sucharow, and a top research integrity expert tells Retraction Watch he sees near-certain signs of fabrication in the data.
Earlier this week, Labaton Sucharow submitted a “citizen’s petition” to the FDA regarding a regulatory filing from Cassava, and called on the agency to halt trials of Cassava’s drug simulfilam on the grounds that it had:
grave concerns about the quality and integrity of the laboratory-based studies surrounding this drug candidate and supporting the claims for its efficacy.
The petition cites three main areas of concern: Unreliable biomarker data, questionable methodology in key experiments and suspect Western blots in papers that constitute the backbone of Cassava’s regulatory finding (along with a grant application to the National Institutes of Health). The articles — which appear in Neuroscience, Biological Psychiatry, PLOS ONE, and other journals, were written by Hoau-Yan Wang, of City University of New York (CUNY), and Lindsay Burns, a Cassava employee.
According to the law firm — which cites this 2016 post on Retraction Watch about work by Elisabeth Bik:
Detailed analysis of the western blots in the published journal articles from Drs. Wang and Burns shows a series of anomalies. The extent of these anomalies forms a 15-year pattern that strongly suggests systematic data manipulation and misrepresentation …
[I]t appears that Drs. Wang and Burns in published PubMed indexed manuscripts and through disclosures with Cassava Sciences have misrepresented preclinical and clinical research results for more than 15 years. This initial examination of their published western blots identified many dozens of examples of protein bands that appear to have been duplicated and/or misrepresented, a Western blot that was used twice to represent different experimental conditions, and a normalization blot that appears to have been manually constructed. Some bands appear to have been “reused” in papers concerning different research topics that were published five years apart.
Cassava has pushed back against the statements, denying any wrongdoing. In a response to the claims of misconduct posted to its website, the company called the allegations “false and misleading.”
Commenters on PubPeer, including Bik, have also flagged papers by Wang and Burns, apparently after the law firm’s letter became public.
David Vaux, deputy director of science integrity and ethics at the Walter and Eliza Hall Institute of Medical Research, in Victoria, Australia, and a member of our parent non-profit’s board of directors, told Retraction Watch:
It is not conceivable that features in the images (such as apparent duplications) arose due to coincidence (chance) or accident, leaving the only plausible explanation being that the images were deliberately falsified or fabricated.
The law firm’s letter makes six recommendations, including an audit by the National Institutes of Health and CUNY of Wang’s work “to determine the existence and extent of data manipulation and possible fraud in all papers and grant applications from Drs. Wang and Burns.” The agency also says it should pause all ongoing trials for simulfilam pending the inquiries, and that the journals “which published the studies discussed herein should review and retract them to correct the public record, if the concerns remain after adequate investigation.”
The company announced two days ago that it had “reached agreement with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for both of its pivotal Phase 3 studies of oral simufilam for the treatment of patients with Alzheimer’s disease.” Last month, experts expressed doubt about some early simufilam data from the company, STAT reported at the time.
Like Retraction Watch? You can make a one-time tax-deductible contribution or a monthly tax-deductible donation to support our work, follow us on Twitter, like us on Facebook, add us to your RSS reader, or subscribe to our daily digest. If you find a retraction that’s not in our database, you can let us know here. For comments or feedback, email us at [email protected].
People, please note Ed Southern invented the “Southern blot” (DNA hybridisation). The term “western blot” was coined to distinguish it from protein detection. Note the capitalisation – this mistake has been made above, unfortunately, but it can also be a paper-mill giveaway in my experience