Praxbind Shows Promise in Brain Hemorrhage Patients

The first reversal agent approved for the anticoagulant dabigatran (Pradaxa) has shown promise in patients with brain hemorrhage.

The first reversal agent approved for the anticoagulant dabigatran (Pradaxa) has shown promise in patients with brain hemorrhage, according to research presented at the American Stroke Association’s 2016 International Stroke Conference.

Idarucizumab (Praxbind) is a humanized monoclonal antibody fragment that binds specifically to dabigatran and its acylglucuronide metabolites. It has an affinity for dabigatran that is about 350 times greater than thrombin’s affinity, and it neutralizes the anticoagulant effect within minutes.

Idarucizumab comes as an intravenous injection that must be refrigerated and administered in a hospital setting. Monitoring parameters include re-evaluation of coagulation through activated partial thromboplastin time, as well as signs and symptoms of clinically relevant bleeding and thromboembolic events.

Patients with hereditary fructose intolerance should not be given idarucizumab because the formulation contains 4 g of sorbitol as an excipient to avoid serious reactions such as acute hepatic failure, hypoglycemia, hypophosphatemia, metabolic acidosis, and uric acid elevations. A thromboembolic risk due to reversal stems from patients having an underlying disease state that predisposes them to those events, and reversal of dabigatran may expose the patient to an elevated thrombotic risk.

Idarucizumab’s duration of effect typically lasts 24 hours. Dabigatran can be reinitiated usually 24 hours after idarucizumab administration, if necessary.

An interim assessment of the first 90 patients in the RE-VERSE AD study showed that idarucizumab rapidly and completely reversed dabigatran’s anticoagulant effects, according to lead study author Richard A. Bernstein, PhD, director of the stroke program at Northwestern Memorial Hospital in Chicago.

This finding comes from an ongoing phase 3 study examining the use of idarucizumab in patients taking dabigatran who have dangerous hemorrhage or require procedures that carry serious bleeding risks. The average participant age was 79 years.

Eighteen patients with intracranial hemorrhage were given 2 infusions of 2.5 g of idarucizumab in a 15-minute period, and all of them saw a total reversal of dabigatran’s blood-thinning effect. Idarucizumab’s ability to reverse this effect quickly and effectively allows clinicians to focus on other areas of care without having to worry about the anticoagulant.

On top of this benefit, idarucizumab does not increase the patient’s tendency to clot. Therefore, perioperative management is simpler and safer.

The biggest challenge in preventing stroke in patients with atrial fibrillation is that nearly half of these patients do not take any blood thinner because of the fear of bleeding. In light of this, idarucizumab may play a role in improving patient compliance and indirectly lead to more stroke prevention by increasing the use of effective blood thinners.

Idarucizumab was approved by the FDA in October 2015 to reverse the anticoagulant effect of dabigatran when patients need emergency surgery or urgent procedures, in life-threatening situations, or when there is uncontrolled bleeding. Prior to idarucizumab’s availability, patients taking dabigatran who required emergency surgery were given purified clotting factors that increased the risk of blood clot formation.