PARIS Three patients treated with an experimental Bristol-Myers Squibb Alzheimer's drug have developed a type of brain swelling known as vasogenic edema, but the side effect may be common in Alzheimer's patients, researchers said on Monday.
Vasogenic edema may even be a sign that drugs are clearing a protein tied to Alzheimer's from the brain, researchers said at the Alzheimer's Association International Conference in Paris.
The results could have bearing on the closely watched drug bapineuzumab, being developed by Pfizer and Johnson & Johnson. Vasogenic edema became a major concern after a 2008 mid-stage study of 240 patients on bapineuzumab found a dozen cases.
But while previous cases of swelling were seen in drugs that use antibodies to remove clumps of the Alzheimer's-related protein beta amyloid from the brain, the Bristol drug BMS-708163 is a gamma-secretase inhibitor that targets the disease with a different mechanism.
"No one had thought this was likely in a trial of a gamma-secretase inhibitor," Dr. Reisa Sperling of Harvard Medical School and Massachusetts General Hospital in Boston told the meeting. She added that the presence of the effect in different classes of drugs showed the side effect may be more common than previously thought.
Sperling said the side effect may be related to the clearing of amyloid from the brain, or it may be these side effects occur spontaneously in patients with Alzheimer's.
Although vasogenic edema was visible on brain scans, none of the patients in the Bristol-Myers study had clinical symptoms and all three had a mutation in the APOE4 gene which raises the risk of Alzheimer's disease.
One of the three patients had signs of brain swelling at the beginning of the study, and Sperling said brain scans showed that patient's condition continued to worsen over the course of the six-month study.
"Whether the treatment increased it, I don't know," she said in an interview.
The field of Alzheimer's research is littered with drug failures, providing little hope to the nearly 36 million people who suffer from it worldwide. Eli Lilly and Co last year halted two studies of its gamma-secretase drug, called semagacestat, after it worsened patients' symptoms of dementia in late-stage clinical trials.
In January, Lilly said one patient in an ongoing trial of its antibody drug solanezumab temporarily developed vasogenic edema, although it was not clear whether the patient was taking the Lilly drug or a placebo.
Concerns over the bapineuzumab study in 2008 prompted the U.S. Food and Drug Administration to issue stricter safety guidelines for clinical trials of drugs that alter amyloid in the brain.
But researchers said last week the FDA agreed to modify those restrictions after a year-long study that showed these types of events may be common in people with Alzheimer's disease.
Sperling said the FDA has been working with researchers and companies to allow more patients to be involved in drug trials for Alzheimer's.
(Reporting by Julie Steenhuysen; Editing by Tim Dobbyn)