Two biotechnology companies recently announced positive initial results in a study of an antibody used to treat Alzheimer’s disease.
There hasn’t been an FDA-approved Alzheimer’s treatment since 2003, according to Ronald Petersen, who directs the Mayo Clinic Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging. Petersen consults with Biogen, a company that specializes in treatments for neurodegenerative diseases and one of the corporations that headed the study.
Alzheimer’s disease is defined biologically by the presence of plaques and tangles in the brain, Petersen said. The plaques are made of a protein called amyloid. The tangles are made of a protein called tau.
In the phase two study, researchers administered an antibody called BAN2401, which was supposed to remove the amyloid protein buildup in the brain, to 856 people.
The goal was to remove plaque — one of the defining characteristics of Alzheimer’s — from the brain.
To get into the study, the patients had to have a PET scan that showed evidence of amyloid in the brain. They also had to be classified as “moderately impaired,” with mild cognitive impairment, but without functional impairment. Patients with mild dementia were also accepted into the trial.
The 856 patients were split into six groups, and five received the antibody. One of the groups received a placebo.
At the end of 18 months, the people who received the highest dose of the antibody declined a bit, Petersen said. But the disease onset was slowed, compared to the placebo group.
“And then when they looked at the PET scans at the beginning and at 18 months, there was less plaque at 18 months than there was at the beginning, implying the drug removed some of the amyloid from the brain,” he added.
So the top-line results are promising, Petersen said, from a clinical and biological standpoint.
Amyloid therapy, a field that received criticism after masses of failed studies, may prove to be one part of a full Alzheimer’s treatment.
However, the full study has not been released — and it could be important to have the full picture.
As far as Petersen knows, Biogen and Eisai looked at the data they’d collected after one year, and didn’t have any positive findings to report.
“However, there was something in the data — apparently — that caused them to go on to 18 months,” he said.
The trial had an adaptive design, Petersen knows, which meant the researchers reallocated people to different groups at the 12-month mark.
“That means if there was one group that didn’t seem to be responding well at all, they would reallocate that group to a higher dose group, or something like that,” he said. “In other words, they made an adjustment mid-course in the study, and apparently this was successful, because the results at the end, at 18 months, were positive when they were negative at 12 months.”
So is all of the data statistically significant?
“I trust it was. They’re not going to put all this money, and effort and time, into something that isn’t defensible in the academic community,” Petersen said. “But again, without seeing the data, we don’t know (everything). … They wouldn’t make a topline announcement without good data.”
There is a 99.6 percent failure rate in studies of dementia treatment drugs.
“The first thing is to drill down on the data,” he said. “If it still holds up, as I suspect it will … What I suspect they’ll do is launch a large phase three trial … with many more subjects, using just that high dose or a couple of doses, and try to establish its efficacy.”