An experimental drug designed to quickly counteract blood-thinning medicines has demonstrated effectiveness, according to preliminary results of a new trial done under real-world conditions.
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."
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.