FDA Approves Idarucizumab, First NOAC Reversal Agent

The US Food and Drug Administration (FDA) today approved idarucizumab (Praxbind, Boehringer Ingelheim) for the reversal of the anticoagulant dabigatran etexilate mesylate (Pradaxa, Boehringer Ingelheim) in patients in need of emergency surgery, urgent procedures, or facing life-threatening or uncontrolled bleeding.

The approval is the first of its kind for a reversal agent of a novel oral anticoagulant (NOAC).

"In the rare event of an emergency situation requiring reversal, treatment decisions must be made quickly and confidently," said Thomas Seck, MD, the vice president of Clinical Development and Medical Affairs at Boehringer Ingelheim Pharmaceuticals, Inc, in a statement. "We believe that the wide availability of Praxbind—and the robust data on its use—can provide patients and healthcare providers with greater assurance in their anticoagulation treatment decisions."

Dabigatran etexilate mesylate was approved in October 2015, based on data from the RE-VERSE AD phase 3 trial, which the FDA also utilized to evaluate its antidote. The trial included 503 patients worldwide at 173 sites, split into 2 groups: Group A (n = 301), in which 60% presented with uncontrolled or life-threatening bleeding, and Group B (n = 202), in which 40% required an invasive procedure or an emergency surgery or intervention.

The final results of the trial were published in the New England Journal of Medicine in July 2017, revealing that in 90 patients that received idarucizumab (Group A, 51 patients; Group B, 39 patients), the median maximum percentage reversal was 100% (95% CI, 100 to 100). Test results were normalized in 88% to 98% of patients, and “evident within minutes,” according to the researchers, measured by ecarin clotting time (ECT, 82%) or diluted thrombin time (dTT, 99%).

After 24 hours, concentrations of unbound dabigatran were below 20 mg/mL in 79% of patients. In Group A, 35 patients could be assessed for hemostasis, which was restored at a mean of 11.4 hours. In Group B, of the 36 patients that underwent a procedure, 33 reported intraoperative hemostasis, 3 patients reported mildly or moderately abnormal hemostasis.

Only a single thrombotic event occurred within 72 hours after idarucizumab was administered to a patient who was not reinitiated to anticoagulants. No adverse safety signals were observed in the study.

Dabigatran etexilate mesylate is widely utilized and stocked in more than 3000 hospitals in all 50 states, according to Boehringer Ingelheim, making the antidote’s approval a welcome sign.

This approval comes on the heels of other anticoagulation news, as just yesterday, Janssen and Bristol-Myers Squibb announced a collaboration that will center on the development and commercialization of Factor X1a (FX1a) inhibitors for the prevention and treatment of thrombotic conditions. Primarily, promising anticoagulant compound BMS-986177 will be advanced into phase 2 clinical trials for broad therapeutic indication consideration under the new partnership.