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 The drug is Portola Pharmaceuticals' AndexXa, known generically as
andexanet alfa. Earlier this month, the U.S. Food and Drug
Administration decided not to approve this so-called reversal agent
without more data. The new test, reported on Tuesday at a European
Society of Cardiology Congress in Rome and released by the New
England Journal of Medicine, offers more evidence. Portola financed
the study.
The drug reversed episodes of major bleeding that couldn't be
stopped because the patients were on drugs such as apixaban and
rivaroxaban, which inhibit the body's natural blood clotting
chemical known as factor Xa.
"There's a big need for a reversal agents for these drugs" that are
being taken by about 2.6 million people, said coauthor Dr. Truman
Milling Jr., an emergency medicine specialist with the Ascension
Seton Dell Medical School Stroke Institute in Austin, Texas.
Such drugs are used by people with conditions such as atrial
fibrillation, which increases the risk of stroke.
Perhaps 1 percent to 2 percent of them will spontaneously start to
bleed somewhere in the body as a side effect of their anti-factor Xa
medicine.
"However, if you didn't give them the anticoagulant, double that
number would stroke. So right there the balance favors
anticoagulation," Milling told Reuters Health in a telephone
interview. "Once they develop a bleed in their brain or they're
bleeding to death, the balance flips the other way."
"Now we need to make them clot again. But not for too long! Because
then they're prone to have strokes and clots and things," he said.
"It's like doing a touch-and-go landing on an aircraft carrier. You
want to use the clotting mechanism just long enough to form a clot
and then take them off again so they're back on the anticoagulant."
Earlier studies of andexanet were done on patients who weren't
bleeding. Researchers looked at markers in the blood to see if
factor Xa suppression was being countered.
"This study was done in patients who were coming to the emergency
room bleeding to death - in hemorrhagic shock, bleeding in the
brain, or bleeding into a critical organ." said Milling. "It's a
much more fraught situation than it is with a normal controlled
healthy population. It's seeing if the drug works on the front
lines, where it can save lives."
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The results reported on Tuesday involved 67 patients who had just
received one of the factor Xa inhibitor drugs and had begun to bleed
dangerously, usually in the brain or the gut. They were followed for
30 days after the episode.
Twelve hours after treatment with andexanet, 79 percent of the
patients were judged to have good or excellent control over the
bleeding. The success rates were comparable for both
gastrointestinal and in-brain bleeding.
However, unwanted blood clots occurred in 18 percent of the
patients, producing one heart attack, five strokes, one lung clot
and seven cases of deep vein thrombosis.
In four of the patients, the clot appeared within three days of
receiving andexanet. In the rest, it surfaced later.
"You can get into a very interesting debate about which complication
is caused by the reversal agent and which is caused by having a
patient on a blood thinner for a reason and then taking him off it,"
Milling said. "I tend to look at the thromboemboli during the first
few days as potentially more likely to be related to the reversal
agent, and there were very few of those."
Fifteen percent of the patients died during follow-up treatment.
Brain bleeding typically kills half the people who develop it,
Milling said. "Any time you study those patients, a lot of them will
die."
The trial, known as ANNEXA-4, is ongoing.
SOURCE: http://bit.ly/2bywXCs New England Journal of Medicine,
online August 30, 2016.
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