Broader results from the ANNEXA-4 trial have confirmed that Portola Pharmaceuticals’ andexanet alfa, sold as Andexxa, can quickly counteract the effects of factor Xa inhibitors such as apixaban and rivaroxaban in most patients, stopping potentially-deadly bleeding.
Preliminary results from 67 patients, released in 2016, found that 79 percent of patients had good or excellent control over bleeding, nearly always in the brain or the gut.
The new results, reported February 7 at the American Stroke Association’s International Stroke Conference in Honolulu and online by the New England Journal of Medicine, cover a broader study population of 352 and show a success rate of 82 percent after 12 hours.
The death rate at 30 days was 14 percent. The 2016 results had pegged it at 15 percent.
The study did not use a control group because of logistical and ethical issues.
“The key here is that blood thinners are good therapies to remove blood clots and it is one of the main therapies in stroke. But bleeding is one of the potential side effects, and the use of this drug can be used to neutralize, right away, potential bleeding problems, if they are spotted.” Dr. Miguel Perez-Pinzon of the University of Miami’s Miller School of Medicine said in a statement released at the meeting.
About 2.6 million people are taking a factor Xa inhibitor, so there is a critical need for an effective reversing agent if bleeding becomes a mortal side effect.
In the study, 55 percent of the volunteers had received apixaban, 36 percent had gotten rivaroxaban, 6 percent were on enoxaparin, and 3 percent had taken edoxaban.
Andexanet reduced anti-factor Xa activity by 92 percent when the anti-clotting agent was apixaban, 92 percent when it was rivaroxaban, and 75 percent when it was enoxaparin.
Eighty percent of the patients were receiving their clot inhibitor for atrial fibrillation. Sixty-four percent of the enrollees had intracranial bleeding and 26 percent of the bleeds were gastrointestinal.
Andexanet was judged to give good or excellent results in 85 percent of the cases of gastrointestinal bleeding and 80 percent of the instances of intracranial bleeding.
Among the 49 patients who died within 30 days of enrollment, 35 succumbed to cardiovascular causes, 12 to non-cardiovascular causes, and two to unknown causes.
The U.S. Food and Drug Administration approved the drug in May 2018. In the study, it was given as a bolus followed by a two-hour infusion, with the doses determined by the type of blood thinner the patient had been taking and an estimate of how much remained in the body.