FDA approves Praxbind (idarucizumab) for reversal of the anticoagulant effects of dabigatran- Boehringer Ingelheim

The FDA has granted approval of Praxbind (idarucizumab), from Boehringer Ingelheim, indicated for patients treated with Pradaxa (dabigatran etexilate mesylate), when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding. This indication is approved under accelerated approval based on a reduction in unbound dabigatran and normalisation of coagulation parameters in healthy volunteers. Continued approval for this indication may be contingent upon the results of an ongoing cohort case series study.

Praxbind was granted Breakthrough Therapy designation, the application received Priority Review and it was approved under an Accelerated Approval Pathway. The application included data from healthy volunteers as well as results from an interim analysis of the RE-VERSE AD trial (NCT02104947). In the studies, the reversal effects of idarucizumab were evident immediately, within minutes after administration of 5 grams of idarucizumab. No procoagulant effect was observed after the administration of idarucizumab. There are serious risks to consider when treating patients with idarucizumab, including warnings and precautions for thromboembolic risk, re-elevation of coagulation parameters, hypersensitivity reactions and risks of serious adverse reactions in patients with hereditary fructose intolerance due to sorbitol excipient. The most frequently reported adverse reactions (at least 5%) in idarucizumab-treated healthy volunteers was headache, and in the Phase III RE-VERSE AD study were hypokalaemia, delirium, constipation, pyrexia and pneumonia.

Comment: RE-VERSE AD, a global study investigating idarucizumab in actual clinical settings, is the only trial to examine patients being treated with dabigatran who are in need of emergency intervention or experience an uncontrolled or life-threatening bleeding event. Boehringer Ingelheim has had to settle 4,000 lawsuits in the US filed over claims about the extent of bleeding risks associated with dabigatran. The company has consistently backed the drug's positive benefit-risk profile, when used as directed, as has the FDA.