$500m Alzheimer’s drug scandal: NY scientist behind NIH-funded therapy busted for allegedly manipulating data in 20 research papers – now there are calls for trials to be cut off

Scientists are calling for phase 3 clinical trials of an Alzheimer’s disease drug to be scrapped after a report revealed serious doubts about the legitimacy of the research that helped the drug reach that stage.

A long-awaited report from the City University of New York (CUNY) accused one of its faculty members, neuroscientist Hoau-Yan Wang, of egregious misconduct involving 20 research papers – defined as workplace conduct so outrageous, dangerous or illegal that a employer cannot reasonably expect that this can be corrected through progressive discipline.

According to the 50-page document obtained by Science, Mr. Wang failed to provide original data to refute allegations that he manipulated images in his research papers, many of which provided crucial support for the lab’s Alzheimer’s drug simufilam’s jump to clinical studies.

CUNY biochemist Kevin Gardner told it Science the report’s findings were “incomprehensibly shameful,” while neuroscientist Matthew Schrag of Vanderbilt University said the ongoing trial “certainly should be halted.”

The accusations were prompted by initial doubts about the doctored images that two scientists put forward in August 2021.

Mr. Wang has long worked with the biotech company Cassava Sciences, whose work on the experimental Alzheimer’s drug simufilam has been heavily criticized.

Simufilam is a drug in tablet form that claims to prevent the buildup of amyloid proteins in the brain, which are a hallmark sign of Alzheimer’s disease.

Along with Wang, Cassava’s senior vice president for neuroscience, Lindsay Burns, is also believed guilty. Burns co-authored some of the papers in question alongside Wang.

The CUNY investigative committee found numerous signs that images in Wang’s research papers were used, cut and pasted and altered multiple times, “presenting falsified or fabricated biochemical data.”

One of the papers in question was a 2012 article published in The Journal of Neuroscience, with both Burns and Wang listed as co-authors, which implied that simufilam might reduce the pathological effects of beta-amyloid, a protein widely believed to that it causes Alzheimer’s disease.

However, the investigative committee could not confirm this a total of 31 allegations against Wang, the majority of which relate to

because he failed to produce the original raw data.

The neuroscientist “could not even provide any data or note in response to any accusation,” the report said.

Wang’s attorney, Jennifer Bothel Scramlin, told Science that neither she nor her client can comment on the report until they speak to CUNY, and that the university has not responded to their questions.

However, CUNY’s report stated that Wang told the university that “a significant number of boxes of research data were discarded in response to a request from CCNY (City College of New York, part of CUNY) to clean the laboratory during the Covid 19 pandemic. .’

The researchers could not find any evidence for this request.

The internal investigation began in the fall of 2021, after earlier allegations were forwarded to CUNY by the Office of Research Integrity (ORI), the government agency that oversees work funded by the National Institutes of Health (NIH).

The NIH gave millions of dollars to Wang and Burns’ work, including about $1.2 million to Wang since December 2020.

According to emails obtained by Science, the investigation was not completed until May of this year.

Four CUNY researchers formed the investigative panel, which was delayed because university officials blocked requests for the image files from Wang’s computers.

This resistance lasted six months and was only resolved after investigators spoke with Vincent Boudreau, the president of CUNY.

Burns and Wang are listed as the joint inventors on multiple patents related to simufilan, and the pair gave intellectual property rights to Cassava Sciences, known as Pain Therapeutics, in 2019.

Doubts about simufilam first arose in August 2021 when an attorney filed a petition to halt clinical trials with the Food and Drug Administrators (FDA) on behalf of two neuroscientists – Geoffrey Pitt of Weill Cornell Medicine and David Bredt, a former pharmaceutical executive .

They wanted the trials stopped because they also doubted the veracity of Wang’s claims in previous research articles.

The petition covered many of the same articles referenced in the CUNY report, which suggested that the alleged image manipulation compromised claims that the drug could slow or even reverse Alzheimer’s symptoms.

Cassava CEO Remi Barbier, Burns’ husband, questioned whether their motives were financial because Pitt and Bredt were short sellers, meaning they could profit when a company’s stock fell.

Barbier also rejected their claims that the data had been manipulated before the trial, and Cassava Sciences filed a defamation lawsuit against the couple and other critics.

In the meantime, investors in Cassava have filed their own lawsuit alleging that executives at the COMPANY, including Burns and Barbier, misled them as part of a “fraudulent scheme” related to simufilam’s likelihood of success.

Cassava conducted small phase 2 trials of the drug in 2019, which he said showed promising results. It then set up the Phase 3 trial needed to gain FDA approval for the treatment of mild to moderate Alzheimer’s.

The company has already signed up more than 800 volunteers and says it will reach nearly 1,100 by December.

After Pitt and Bredt’s petition, the FDA refused to stop the trials.

Mr. Schrag told Science that he first provided information to the NIH about Wang’s studies during the summer of 2021.

He said CUNY’s report is “detailed, thorough and credible.”

“But a two-year delay is somewhat surprising. … The Phase 3 clinical trials of simufilam should never have begun. And based on this report, they should certainly be closed down.”

CUNY has taken no public action regarding Wang in the nearly five months since the report was completed.

Senior Advisor to the CCNY President Dee Dee Mozeleski told Science that Boudreau could not comment on the matter at this time, but said that “action on the report is imminent.”

Cassava Sciences also declined to comment on the report to Science, saying the university had not sent it to the company.

It says CUNY has not spoken to any Cassava employees as part of the process and has “declined all requests for information and offers of assistance from Cassava.”

The biotech company added that it “looks forward to continuing the development of simufilam as a potential treatment for patients with Alzheimer’s disease.”

CUNY biochemist Kevin Gardner, who assisted with an initial evaluation of Wang’s work, but was not part of the final review, told Science what the panel found “incomprehensibly shameful.”

He said Dr. Wang’s research results were “atrocious,” adding that the fact that his work supported clinical trials is “doubly sickening.”