ACC: New findings presented on dabigatran antidote

March 31, 2014

Idarucizumab (Fab, Boehringer Ingelheim), an investigational humanized antibody fragment being studied as a specific antidote for dabigatran (Pradaxa), reversed dabigatran anticoagulation, even in the presence of elevated dabigatran levels and life-threatening bleeding from severe trauma, in animals, according to a study presented at the American College of Cardiology 63rd Annual Scientific Session (ACC.14), Washington, D.C.

Idarucizumab (Fab, Boehringer Ingelheim), an investigational humanized antibody fragment being studied as a specific antidote for dabigatran (Pradaxa), reversed dabigatran anticoagulation, even in the presence of elevated dabigatran levels and life-threatening bleeding from severe trauma, in animals, according to a study presented at the American College of Cardiology 63rd Annual Scientific Session (ACC.14), Washington, D.C.

In animals that received dabigatran without an antidote, blood loss was significantly increased at 10 minutes after injury compared to animals not given dabigatran. For all animals that did not receive the antidote, there was 100% mortality, with a mean survival time of 121 minutes.
 
Treatment with idarucizumab was associated with a dose-dependent reduction in blood loss and mortality. The lowest dose of antidote, 30 mg/kg, reduced blood loss (mean=1,705 mL), and reduced mortality to 17%, or 1 out of 6 animals. Blood loss was further reduced in animals receiving 60 mg/kg (mean=1,077 mL) or 120 mg/kg (mean=1,137 mL) of antidote, with all animals surviving. No adverse events were observed following treatment with idarucizumab.

 

Although this is a preclinical study of an investigational drug, these new findings represent an important step in the development of a specific antidote for dabigatran, according to one of the authors of the study Joanne van Ryn, PhD, dabigatran scientific support, Boehringer Ingelheim, CardioMetabolic Disease Research, in Germany.

“Currently, there are no specific antidotes available for any of the new oral anticoagulants to complement the existing range of bleed management options during critical care situations,” van Ryn said. “Standard clinical support for bleeding is similar for anticoagulant treatments. Bleeding management for anticoagulant patients may include applying direct pressure to the site of the bleeding, administering fluids and/or blood products--for example, blood transfusions--as needed, and stopping the bleeding through surgery.”

The clinical development of idarucizumab is ongoing. Boehringer Ingelheim is sponsoring 3 placebo-controlled phase I trials with idarucizumab in healthy volunteers. (Clinicaltrials.gov identifiers: NCT02028780, NCT01955720, and NCT01688830)