Experimental drug may slow spread of sepsis
WASHINGTON, Sept. 14 (UPI) -- An experimental, genetically engineered compound
that mimics the body's immune system somewhat reduced both death and amputations
caused by a rare but aggressive type of infection commonly called
meningococcemia, according to a new study.
The infection, also called meningoccocal sepsis. "cuts down healthy kids and
kills or maims them in 24 hours or less," said researcher Dr. Breff Giroir of
Children's Medical Center in Dallas.
In a multi-center international study, the new drug, called
bactericidal/permeability-increasing protein (BPI) had mixed results, said
Giroir.
"Children who received BPI had a lower incidence of amputations and had a better
overall functional outcome," says Giroir. But compared with placebo, the
mortality rate in the treatment arm was only slightly better -- 7.4 percent
compared to 9.9 percent in the placebo group.
"The mortality difference did not reach statistical significance and that is
disappointing," said Giroir, who will publish the findings in the Sept. 16 issue
of The Lancet.
The bacteria that causes the infection responds well to antibiotics, said
Giroir. But even as the antibiotic attacks and kills the bacteria, blood cells
already are circulating harmful byproducts of the bacteria. Called endotoxins,
these bacterial byproducts in the blood very quickly take over and destroy
healthy tissue, says Giroir.
"This leads to gangrene and amputations. Children who are lucky enough to
survive often leave the hospital without hands and feet," he said.
The experimental drug BPI, also named Neuprex, is actually a copy of a protein
made by the body's white blood cells, the structures that naturally attack
infections.
BPI has not been approved by the Food and Drug Administration, which ruled in
April that study results were "not sufficient to support the filing."
Manufacturer XOMA Ltd of Berkeley, Calif., and Giroir himself said they plan
both to work in providing further data and in appealing the ruling.
In the study of 393 children treated at 22 centers in the United States and
Britain, patients were randomized to either receive the BPI plus antibiotic
therapy or placebo plus standard antibiotic treatment.
Giroir said one reason for the poor mortality result was "that we excluded those
patients who were facing imminent death. As a result, the mortality in both arms
was much lower than predicted and that may affected the ability to demonstrate a
benefit."
He said expected mortality for severe meningoccocemia is about 20 percent.
He said, too, "the BPI may not have been administered quickly enough. Sixteen
patients who were selected for the study died before we could actually get the
IV going," he said.
In a commentary that accompanies the study, Dr. Marcel van Deurent of University
Medical Center, Nijmegen, Netherlands, agreed that the results would probably be
more impressive if the drug was given sooner.
Cutting the time to treatment is, however, very difficult says Giroir because
the disease progresses so quickly.
"It starts like a flu with mild fever, nausea, vomiting-nothing very specific,"
he said. "But when purple spots appear on the skin-we call these purpura, it
progresses very, very rapidly." Dr. Blaise Congeni, a pediatric infectious
disease specialist at Akron Children's Medical Center in Akron, Ohio, said he
and others in the infectious disease community have been "talking about this
sort of approach -- anti-endotoxins -- for about a decade. We need something to
use within those critical first few hours, something more than an antibiotic,
because even if we can kill the bacteria, those bacteria have been producing
endotoxins for a few hours."
Congeni said meningcoccal sepsis "is rare but an infectious disease, of which a
specialist at a major referral center will see a couple dozen cases a year."
Giroir said the infection tends to "occur in clusters. In the United States
there are about 3,000 cases year. There has been an upsurge since the 1990s and
it is a very significant health problem in the United Kingdom with about 4,000
cases a year."
He said that in the United States there are "clusters in Texas, Oklahoma and
Florida, but the biggest cluster is in the Pacific Northwest -- Washington and
Oregon." (Reported by Peggy Peck in Cleveland.) |
