* Brain swelling problem may decrease over time
* Drug well tolerated in long-term study
* Some cases of mild vasogenic edema were undetected
* Studies may build confidence in once-battered drug
By Julie Steenhuysen
PARIS, July 20 Experimental Alzheimer's drug
bapineuzumab, from Pfizer (PFE.N) and Johnson & Johnson
(JNJ.N), may be safer than originally thought, according to two
studies by U.S. researchers released on Wednesday.
They said that a brain swelling condition called vasogenic
edema, which caused a lot of worry over the drug's safety early
on, may decrease over time.
"It looks like we can treat people for a number of years
safely," Dr. Steven Salloway of Butler Hospital and Brown
University in Providence, Rhode Island, told the Alzheimer's
Association International Conference in Paris.
Salloway looked at the long-term safety of 194 patients in
a mid-stage trial of the drug that stayed on treatment after
the initial phase ended. Of those, 86 patients got the drug for
at least 3 years and 43 were treated for at least 4 years.
About 24 percent of the patients had side effects possibly
related to the drug, and some 85 percent of these were
considered mild to moderate.
Cases of vasogenic edema, now called ARIA-E or Amyloid
Related Imaging Abnormalities with Parenchymal Edema, appeared
to lessen over time.
The risk of developing ARIA-E dropped from 6.7 percent in
the first three infusions of the drug, to 2.7 percent for the
fourth through the 10th treatment.
"That is very encouraging to me," Salloway said in an
interview. "I think this is a transient condition."
"We've treated a lot of patients at at our center. I think
it is very well tolerated," he said.
Larger, late-stage clinical trials will be needed to
determine whether the drug works. Those studies are expected to
stop enrolling patients in mid-2012.
There is no current treatment for Alzheimer's, which
affects nearly 36 million people worldwide.
SWELLING WITHOUT SYMPTOMS
In a separate study of the drug, a team led by Dr. Reisa
Sperling of Brigham and Women's Hospital and Harvard Medical
School in Boston reviewed more than 2,000 MRI scans from 262
patients who participated in mid-stage studies of
She looked for cases of amyloid-related abnormalities on
the scans that might represent vasogenic edema or tiny leaks in
The radiologists in the study were specifically looking for
amyloid abnormalities in the brain that might have gone
undetected because patients had no symptoms.
The team found 36 cases thought to be linked to treatment
with bapineuzumab, including 15 new cases. None of these
patients had symptoms of ARIA-E, which can include headache,
memory loss, loss of coordination and disorientation.
Since these cases were not identified, many of these
patients continued to be treated with bapineuzumab.
"They were treated through their ARIA and remained
asymptomatic," Sperling said in an interview.
"For me that was reassuring. You see these changes in the
MRI and they look a little frightening. The fact that they can
potentially be treated and remain OK is reassuring."
The team also found that people treated with higher doses
of bapineuzumab who have an Alzheimer's risk gene called APOE-4
tend to have more ARIA-E side effects, confirming the
companies' decision to lower the dose of the drug in these
Salloway said the mid-stage study he looked at was not
meant to show whether the drug helped improve clinical
symptoms, but the researchers were encouraged to see it appears
to be safe.
Many researchers think patients with mild to moderate
Alzheimer's disease are too far gone to have any significant
benefit from drugs like bapineuzumab.
Salloway says he is hopeful the drug will work, but he will
not fret if the late-stage results do not improve symptoms.
"I don't think it would kill the drug or the amyloid
hypothesis," he said. Drugs like bapineuzumab remove deposits
of beta amyloid from the brain, on the theory that will help
improve memory problems in people with Alzheimer's disease.
Despite several attempts, no anti-amyloid drug has shown a
benefit, but all of them have been tried in people with more
Researchers are now looking for safe ways to test people in
the earliest stages of Alzheimer's, in some cases even before
J&J and Pfizer are developing bapineuzumab jointly. Elan
Corp ELN.I, one of the drug's original developers, still
retains a financial stake.
(Editing by Bernard Orr)