Cerebral edema occurred far more frequently than previously reported in clinical trial participants treated with bapineuzumab, researchers said.
Bapineuzumab is the investigational biologic drug that scavenges beta-amyloid plaques in the brain, Med Page Today reports.
Reisa Sperling, MD, MMSc, of Brigham and Women's Hospital in Boston, was involved in the research.
She said a central review of brain images from 262 patients identified 15 previously undetected cases of vasogenic edema, along with the 21 cases identified earlier.
But another study presented indicated that the risk of edema seems to decrease over time in patients who remain on the drug.
The specific risk of edema that researchers were concerned about is amyloid-related imaging abnormalities of edema/effusion, or ARIA-E.
Bapineuzumab is a monoclonal antibody tailored for beta-amyloid protein plaques. Animal studies and limited human data have indicated that it wipes plaques from the brain.
But the product’s safety has been called into question following the edema reports and the subsequent concerns, reports Med Page Today.
The review described by Sperling covered participants in three phase II trials. Phase III studies were already underway when the initial findings of edema were reported.
As a result, investigators were forced to drop the highest dose level under evaluation. Those studies, as well as an open-label extension of one of the phase II trials, are continuing.
Sperling spoke at a press briefing prior to her scheduled presentation at the Alzheimer's Association International Conference on Alzheimer's Disease.
She reported that all of the 15 newly identified cases were asymptomatic, including 13 who received multiple doses without apparent problem.
Small hemorrhages were also visible on the image review in 17 of the cases. Sperling said this was consistent with the edema, insofar as both essentially result from "leaky vessels."
Also at the press briefing, Stephen Salloway, MD, of Brown University in Providence, R.I., reported data from the phase II extension study, Med Page Today reports.
The phase II study indicated that the risk of edema appears to be concentrated early in treatment.
Dubbed Study 251, the trial treated 194 patients who received one of three doses of bapineuzumab IV ranging from 0.15 to 1.0 mg/kg every 13 weeks. Patients receiving 2.0-mg/kg in the original study were switched to 1.0 mg/kg because the higher dose was discontinued.
Salloway said that signs of edema on imaging were seen in 6.7% of patients after the first three infusions. But for the fourth through 10th infusions, the edema rate was only 2.7%.
He suggested that the edema is probably tied to the drug's clinical effect in clearing plaques in the early stages of treatment, reports Med Page Today.
Sperling considered the new findings to be positive for bapineuzumab's future prospects.
She added that the "leaky vessel" problem is most likely a class effect for plaque scavenging agents.
"We'll have to wait and see in the phase III what the results show," Salloway said, Med Page Today reports.
