A small company that trumpeted an exciting new treatment for Alzheimer's disease is now under fire after several studies were questioned by scientific journals.
The company, which is based in Austin, Texas, announced last summer that its drug, simufilam, improved cognitive function in Alzheimer's patients in a small clinical trial. A larger trial was initiated by Cassava.
The potential of the drug attracted a lot of attention. Alzheimer's disease affects six million Americans and is expected to double by the year 2050. At one point, the stock soared by more than 1,500 percent. The company was worth $5 billion last summer.
Many scientists have been skeptical of the company's claims, asserting that their studies were flawed and that their results were not reliable.
Some trial participants' families say they see improvements. Critics said that the Alzheimer's patients were not followed long enough to confirm that improvements in cognitive function were genuine, and that the trial reporting better cognitive function due to simufilam lacked a placebo group.
The company was accused of manipulating its scientific results by some experts.
The Journal of Neuroscience published "expressions of concern" regarding two brain studies authored by the company's chief researcher, Hoau-Yan Wang, a professor at the City University of New York. Lindsay H. Burns is the chief scientist at Cassava. Errors were noted in the images accompanying the study.
The expression of concern indicates that the editors have reason to question the integrity and accuracy of the paper.
The journal Neurobiology of Aging attached an expression of concern to a publication about Alzheimer's authored by Dr. Wang and Dr. Burns.
The editors did not find compelling evidence of data manipulation intended to misrepresent the results, but they did find a number of methodological errors. The journals said they would wait for the investigation to be finished.
Dr. Wang didn't reply to requests for comment. The university wouldn't confirm or deny that an investigation was underway.
A spokesman for the journal said that five papers by Dr. Wang had been withdrawn after a five-month investigation. Two of the papers were written by Dr. Burns and focused on a brain protein.
The experts were contacted by the New York Times. They didn't trust the company's methods, results or even the premise of the drug's supposed effectiveness.
The University of California, San Francisco's Dr. Roger Nicoll is angry that his work is partly funded by taxpayers. The company has received more than $20 million from the National Institutes of Health.
This drug should not be used in patients. It should not have been. The longer this goes on, the more enraged I am.
Many of the critics of the company were bad actors with financial conflicts of interest, according to the company's founder and chief executive. He said that the allegations of data manipulation were false, and that they were publicized by short sellers to drive down the company's stock price.
Mr. Barbier wrote in an email that the effort to besmirch Cassava Sciences appears endless.
There is a new entrant to Alzheimer's research. Remoxy was a favorite among investors because it was intended to deter drug abuse.
The company was reprimanded by the FDA for promoting Remoxy before approval.
simufilam restores the normal shape and functioning of aprotein called filamin A that becomes warped in the brains of people with Alzheimer's disease.
Alzheimer's experts said there were no independent studies that supported this hypothesis.
The overall conclusions with regard to Alzheimer's disease make no sense to me.
His theories are implausible and contrived, and they are not in the mainstream of the field.
The theory is supported by strong evidence, according to the papers.
The criticisms have hurt the reputation of Cassava. The company told investors that only 60 of the 1,750 people it needed for the trial had been signed up. The company's stock was trading at $25 per share on Monday, down from a high of $135 last summer.
The object of short-selling tactics has been Cassava. Two scientists filed a citizen's petition to the F.D.A., using a law firm that represents whistle blowers and citing grave concerns about the quality and integrity of the project. Its stock fell by 30 percent.
Both scientists profited from the stock's decline, which undermined the credibility of their petition. Both have sold their financial positions.
The F.D.A. denied the petition because it was not the appropriate subject of a citizen petition.
F.D.A. officials acknowledged the issues raised and said its response did not represent a decision by the agency to take or refrain from taking any action.
The F.D.A. does not discuss possible or ongoing investigations, according to a spokeswoman.
According to The Wall Street Journal, the company is being investigated by the Securities and Exchange Commission. Mr. Barbier acknowledged that the National Institutes of Health is also investigating.
In a securities filing in November, the company said it was cooperating with certain government agencies that were looking for corporate information and documents.
No government agency has told the company that any wrongdoing has occurred.
Two-thirds of patients who took simufilam for a year had an improvement in their cognitive function. The company reported that some of the 50 patients had no neurological or psychiatric symptoms by that time.
The study did not compare the medication to a placebo. All of the participants in this trial received the drug and were aware of it, and their reported improvement could have been a result of their positive expectations.
Robert Howard, professor of old age psychiatry and an expert in clinical trial design at University College London, said that a drug to improve cognitive scores would have to have an extraordinary effect on reversing neurodegeneration.
He said that slowing or stopping of cognitive decline is a win. He said that it is implausible to claim that patients are improving on the basis of small numbers.
The data from the trial that did include a placebo group was reanalyzed by an outside lab. The company acknowledged that the second analysis was done by its partner.
If the data is suspect in key papers, and not just minor mistakes, you can't trust anything, said George Perry, a neuroscientist at the University of Texas at San Antonio and editor in chief of The Journal of Alzheimer.
Several methodological quirks were pointed out by experts. Changes in the levels of certain molecules in the C.S.F. are evidence of simufilam's effectiveness.
The testing method used by the company is out of range, according to Dr. William Hu, an expert on spinal fluid markers at Rutgers.
There is a clear discrepancy between what is reported for Alzheimer's disease patients and what is reported for C.S.F. markers.
The company uses an outdated lab technique called Western blotting, which does not have the sensitivity or accuracy of newer methods.
Data from another set of experiments shows that the drug can restore the shape of filamin A in the brain.
He said there was no way this could happen.
After short sellers filed the F.D.A. petition, a leading expert in image manipulation became aware of the company. Dr. Bik pointed to signs that the results had been copied and pasted from other experiments in a series of posts on her website.
She said in an interview that those were of severe concern. It is highly likely that there was some manipulation going on, based on the pattern ofIrregular images in multiple papers.
Charles Spruck, a cancer researcher at the San Diego-based Sanford Burnham Prebys Medical Discovery Institute who has more than 25 years of experience with the Western blot method, said he believed the anomalies in the images could be the result of simple mistakes.
Irregularities or errors in one or two images could be due to chance, but when you see it again and again, it makes it unlikely that you could do it accidentally, said Dr. David Vaux, deputy director of scientific integrity.
The company's research findings were unaffected, Mr. Barbier said.
Many scientific journals are reluctant to withdraw papers because of their fear of being sued, or damage to their own reputations, because of the limitations of peer review in identifying mistakes or manipulation.
The peer review process seems to have taken it as far as it can, so it is time for regulatory bodies to step in.
All Rights Reserved © 2024
