Experimental Alzheimer's Drugs Found Ineffective in Clinical Trials
WEDNESDAY, Jan. 22, 2014 -- Two experimental drugs for Alzheimer's disease have failed their clinical trials, proving unable to help patients with mild to moderate dementia, according to new studies.
Both bapineuzumab and solanezumab did not improve patients' ability to think and solve problems, according to findings published in the Jan. 23 issue of the New England Journal of Medicine.
The drugs were intended to help people with Alzheimer's by clearing the amyloid beta protein plaques that typically clog neurons in the brains of people with the degenerative illness, the researchers said.
Neither medication improved patients' ability to think. "We were disappointed there was no clear clinical benefit," said Dr. Steven Salloway, lead researcher on the bapineuzumab study. Salloway is a professor of neurology and psychiatry at the Warren Alpert Medical School of Brown University.
Despite these findings, Salloway and other Alzheimer's researchers still believe research should continue on amyloid beta, given how prevalent it is in the brains of Alzheimer's patients.
Heather Snyder, director of medical and scientific operations for the Alzheimer's Association, said these types of drugs might be more effective if they are used to prevent Alzheimer's rather than treat it.
Snyder explained that amyloid plaques begin forming in the brain years before a person begins having symptoms.
"The underlying biology of what we see is occurring a decade or more before people have the clinical symptoms," she said. The theory is that by giving people anti-amyloid medications at that early stage, doctors might be able to prevent the onset of Alzheimer's.
The two medications are called "antibody" drugs. They both work by binding to amyloid beta and helping flush it out of the brain and body.
Hopes were riding high on these medications, which were given thorough clinical trials. The solanezumab trial involved more than 2,000 people, while the bapineuzumab trial included more than 2,200 people.
Bapineuzumab appeared to reduce amyloid buildup in patients, but amyloid continued to increase in patients treated with solanezumab.
Most crucially, neither drug had any effect on patients' ability to think or conduct activities of daily life.
Researchers did learn some things despite this setback, said Salloway, who is also director of neurology and the memory and aging program at Butler Hospital in Providence, R.I.
Both drugs were administered intravenously, and the clinical trials showed that this is an effective way to deliver medication. "We didn't know how Alzheimer's patients would tolerate frequent intravenous treatment, and they tolerated it very well," he said.
In addition, the bapineuzumab trial showed that medication can be used to effectively slow amyloid buildup, leading some doctors to believe that it could serve as a preventive treatment for people at risk of Alzheimer's.
"I know the consensus from the field is that amyloid plays an important role early in the disease process, so the earlier we can treat it the better the benefit," Salloway said. "We're hoping the use of these medicines earlier on will have more benefit."
According to news reports, Eli Lilly is planning another trial of solanezumab, despite these results. Pfizer, the maker of bapineuzumab, is not pursuing further research into its new drug.
Future research might need to shift focus toward combination therapies like those used to treat HIV, Salloway said.
"This will involve a little more creativity in drug development. Companies will have to cooperate and share data," he said. "We also need to have drugs that will lower amyloid more dramatically than they did in this trial."
Although research should continue to focus on amyloid, Snyder said, the Alzheimer's Association has always funded research into other potential treatments.
"It's really important to continue to research a number of different mechanisms that could explain Alzheimer's," she said. "We can understand more about how the immune system is involved, for example. It's important to understand what is happening during Alzheimer's."
For more information on medication for Alzheimer's disease, visit the Alzheimer's Association.
Posted: January 2014