* Three cases now seen in Bristol-Myers' drug BMS-708163
* Problem seen on brain scans; patients had no symptoms
* Condition may be common treatment side effect-expert
By Julie Steenhuysen
PARIS, July 18 Three patients treated with an
experimental Bristol-Myers Squibb (BMY.N) 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, U.S.
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
The results could have bearing on the closely watched drug
bapineuzumab, being developed by Pfizer (PFE.N) and Johnson &
Johnson (JNJ.N). Vasogenic edema became a major concern after a
2008 mid-stage study of 240 patients on bapineuzumab found a
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 (LLY.N) 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
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
Sperling said the FDA has been working with researchers and
companies to allow more patients to be involved in drug trials
(Reporting by Julie Steenhuysen; Editing by Tim Dobbyn)