A drug touted by a small pharmaceutical company as a treatment for Alzheimer’s disease has had a turbulent bid for regulatory approval.
Studies that once seemed to support the drug, simufilam, have been called into question, leading to retractions from scientific journals and resignations of top officials at Cassava Sciences, the company sponsoring it.
In September, the Securities and Exchange Commission brought charges against Cassava Sciences, alleging that the company had made misleading statements about the results of clinical trial data. The S.E.C. also charged a Cassava consultant researcher for manipulating research results.
Cassava Sciences agreed to a $40 million settlement with regulators to resolve the case; the company neither admitted nor denied wrongdoing.
Yet to the consternation of some dementia experts, simufilam remains in advanced clinical trials. “If the efficacy and the underlying data is being questioned, which it is, why would you continue the study?” said George Perry, an Alzheimer’s researcher at the University of Texas at San Antonio.
While some important results have been challenged, the company maintains there are still research and clinical results that suggest the drug may yet prove valuable.
The company said that more than 1,900 patients with mild to moderate Alzheimer’s disease are currently enrolled in Phase 3 clinical trials, typically the last evaluation before the Food and Drug Administration decides whether to approve a medication for public use.
The F.D.A. has the authority to pause or end clinical trials, and “may take appropriate action” to protect participants if it becomes aware of data falsification after a detailed review, a spokeswoman for the agency said.
But the agency does not comment on ongoing clinical trials or ongoing investigations, she added.
The F.D.A. might be more willing to allow the trial to go on because its participants are not forgoing other options for Alzheimer’s treatment by enrolling, said Nathan Cortez, a professor at the Southern Methodist University Dedman School of Law who researches food and drug regulation.
Cassava has promoted simufilam as a potential breakthrough drug for Alzheimer’s disease, which affects more than six million Americans and has virtually no effective treatments.
Scientific studies in reputable journals supported the drug’s new treatment mechanism and the company boasted impressive results from its clinical trials, suggesting that the drug significantly slowed cognitive decline. Cassava was at one point worth nearly $5 billion.
The reputation of the drug and the company has since fallen.
Hoau-Yan Wang, a former Cassava adviser and a scientist who published key papers describing the drug’s ostensible mechanisms, was indicted on charges of falsifying data by a federal grand jury. An investigation by the City University of New York concluded that he had engaged in “significant research misconduct.”
He is now on administrative leave from his appointment at CUNY, according to a university spokesman. The university declined to comment on internal or external investigations.
Several of Dr. Wang’s papers have been retracted, and scientific journals have published “expressions of concern” about others, a notice that indicates editors have reason to question the integrity and accuracy of a study.
Remi Barbier, the company’s chief executive, and Lindsay Burns, a lead scientist and Mr. Barbier’s wife, resigned from Cassava shortly after it was reported that the S.E.C. had begun an investigation.
Last week, the S.E.C. announced it had charged the company, Mr. Barbier and Dr. Burns for making misleading claims about simufilam’s effectiveness. The agency alleged that Cassava cherry-picked data to support its claim that the drug had produced significant memory improvement in an earlier clinical trial.
In fact, the full set of data showed “no measurable cognitive improvement,” the S.E.C. reported. The agency alleged that Dr. Wang, who was also charged, manipulated data to make the drug appear more effective than it was.
Despite these developments, the company said it was optimistic that its current trial would show that the medication is effective.
In a statement, a spokesman for Cassava said that the S.E.C.’s charges related to inadequate securities disclosures were not meant to make a judgment about the scientific evidence surrounding simufilam.
“We won’t know the results of our first Phase 3 study until later this year, but we believe there are good reasons to believe our trial could be successful,” Rick Barry, the company’s recently appointed chief executive, said in a statement.
Routine safety evaluations of the company’s trial by an independent group of experts have not found evidence that the drug poses health risks that warrant a change to the trial, the statement said.
But Dr. Perry said safety is just one piece of the puzzle.
In clinical trials so advanced, there should at least be some convincing evidence that the drug is also effective, he said.
And Dr. Roger Nicoll, a neuroscientist at the University of California, San Francisco, said that continuing the trials without an adequate research foundation could come at a cost: “It is a waste of money, and it is maintaining a false hope.”
The F.D.A. stops about a hundred trials every year for any number of reasons, including fraud, Dr. Cortez said. Even if the simufilam trial is allowed to finish, the F.D.A. may decide to reject the data if it is deemed untrustworthy, he noted.
“The F.D.A. is not afraid to put clinical hold on, and it has the authority to do so,” Dr. Cortez said. “I’m not quite sure why it’s taking so long, given the amount of scrutiny on this particular drug.”
