A biotech company’s attempt to produce a treatment for Alzheimer’s disease is now likely to end in disastrous fashion. This week, Cassava Sciences reported the failure of its latest Phase III trial of its experimental drug, simufilam—a drug that allegedly got as far as it did due to poorly done and potentially fraudulent research surrounding it.
On Monday, Cassava Sciences announced the topline results of its year-long randomized, controlled trial of simufilam, which tested whether the twice-daily pill could be effective at slowing down the progression of dementia in people with mild to moderate Alzheimer’s. Simufilam failed to meet any primary or secondary goals of the study, essentially meaning it performed no better than placebo across the board. The results look to be the final nail in the coffin for Cassava’s development of the drug, which has long been marred by allegations of fraud committed both by affiliated researchers and Cassava executives.
In particular, outside scientists and federal agencies have accused Hoau-Yan Wang, a City University of New York (CUNY) professor and former Cassava advisor, of repeatedly committing scientific misconduct during his research on simufilam for the company. This misconduct may have gone as far as Wang manipulating images and skewing or outright fabricating results to make the drug look more promising. While Wang may have been responsible for the most egregious acts of bad science tied to simufilam, though, critics have also argued that Cassava misled the public itself.
Earlier this September, the company agreed to pay more than $40 million to the Securities and Exchange Commission to settle charges related to its handling of the Phase II trials on simufilam, while Wang agreed to pay $50,000 in fines. According to the SEC, Wang was able to identify whether some of the patients were taking a placebo or the experimental drug (in pivotal clinical trials, scientists are normally kept in the dark about this distinction, since it could bias their analysis); Wang then allegedly used this information to make simufilam look much more effective at improving biomarkers related to Alzheimer’s disease. The SEC further alleged that Cassava and its former CEO, Remi Barbier, and its former Senior Vice President of Neuroscience, Lindsay Burns, made misleading statements based on the Phase II results to its investors. In one alleged instance, Cassava claimed that simufilam significantly improved patients’ episodic memory, while failing to disclose that this improvement was only found in a subset of patients selected by Burns, and that no such improvement was seen in the full set of patient data.
In settling with the SEC, Cassava, its executives, and Wang did not admit or deny the allegations made against them. Following the SEC’s charges, Cassava claimed that it cooperated with the investigation and that it was taking steps to prevent any further research issues; the company also stated that Wang had zero input on the Phase III trials of simufilam. But critics have alleged that the misconduct and inflated claims surrounding simufilam date back far earlier than the Phase II trials, suggesting that the drug never worked as intended. Given these latest findings, the critics look to have been right.
Cassava seems to have staked its future on the success of simufilam, since it has no other drug candidates in the pipeline—a future that’s now in peril, to say the least. In the wake of the drug’s failure, the company announced that it would be ending its second Phase III trial of simufilam early, though it reportedly still plans to release the data from both trials to the public. As for Wang, his legal troubles aren’t necessarily over. Earlier this June, a federal grand jury in the District of Maryland indicted Wang for allegedly defrauding the U.S. National Institutes of Health (NIH) of approximately $16 million in federal grant funds, which appears to be tied to his Alzheimer’s research.
