Controversial Alzheimer’s drug burned down

A biotech company’s attempt to develop a cure for Alzheimer’s disease is likely to end disastrously. This week, Cassava Sciences announced the failure of its latest Phase 3 study of its experimental drug, simufilam, a drug that supposedly made it this far because of poorly done and potentially fraudulent research on it.

Cassava Sciences on Monday announced key results from a year-long, randomized, controlled trial of simufilam, which tested whether a twice-daily pill might be effective in slowing the progression of dementia in people with mild to moderate Alzheimer’s disease. Simufilam did not meet any of the study’s primary or secondary goals, which essentially means it did no better than placebo in all areas. The results appear to be the final nail in the coffin of Cassava’s development, which has long been marred by allegations of fraud by both affiliated researchers and Cassava executives.

Especially, external scientists AND federal agencies accused Hoau-Yan Wang, a City University of New York (CUNY) professor and former cassava adviser, of repeatedly making scientific errors while conducting simufilam research for the company. This misconduct may have gone as far as Wang manipulating images and distorting or outright falsifying results to make the drug look more promising. While Wang may have been responsible for the most egregious acts of bad science related to simufilam, critics also argued that cassava misled the public itself.

At the beginning of September this year, the company Agreement to pay more than $40 million to the Securities and Exchange Commission to settle charges related to its conduct of Phase II trials of simufilam, while Wang agreed to pay a $50,000 fine. According to the SEC, Wang was able to determine whether some patients were taking a placebo or an experimental drug (in pivotal clinical trials, researchers typically do not know this distinction because it could bias their analysis); Wang then allegedly used this information to make simufilam much more effective at improving biomarkers associated with Alzheimer’s disease. The SEC further alleged that Maniok and its former CEO Remi Barbier and former senior vice president of neurology Lindsay Burns made misleading statements to investors based on Phase II results. In one alleged case, Cassava claimed that simufilam significantly improved patients’ episodic memory, without disclosing that this improvement was only found in a subset of patients selected by Burns and that no such improvement was observed in the full patient data set.

In reaching the settlement with the SEC, Cassava, its executives and Wang neither admitted nor denied the allegations against them. Following the SEC’s allegations, Cassava claimed that it cooperated with the investigation and took steps to prevent further research problems; the company also said Wang had no input into the Phase III study of simufilam. However, critics allege misconduct and inflated claims regarding simufilam date back much earlier than Phase II trials, suggesting the drug never worked as intended. Given these latest findings, it seems the critics were right.

Maniok appears to have staked its future on the success of simufilam, as it has no other drug candidates in the pipeline – a future that is now at risk, to say the least. In the wake of the drug’s failure, the company announced it would end its second Phase 3 trial of simufilam early, although it reportedly still plans to release data from both studies to the public. As for Wang, his legal troubles aren’t necessarily over. In early June of this year, a federal grand jury in the District of Maryland accused Wang for allegedly defrauding the U.S. National Institutes of Health (NIH) of approximately $16 million in federal grant funds, which appears to be related to his Alzheimer’s disease research.