Boehringer Ingelheim Initiates Trial Of Idarucizumab To Reverse Pradaxa

Boehringer Ingelheim announced that it has started a trial of idarucizumab at U.S. sites. The company announced the study initiation in a press release, stating that the RE-VERSE AD trial is a phase 3 study in over 35 countries with an expected enrollment of 250 patients. The study is investigating idarucizumab as an antidote to Pradaxa (dabigatran etexilate mesylate), a newer oral anticoagulant.

Lead investigator Dr. Charles Pollack, from the University of Pennsylvania, said, “Studies of idarucizumab in animal models and in healthy human volunteers suggest that administration of idarucizumab results in immediate, complete, and sustained reversal of the anticoagulant effects of Pradaxa.”

Idarucizumab

Idarucizumab, the proposed International Nonproprietary Name (pINN), is a humanized antibody fragment (Fab). The Food and Drug Administration granted Breakthrough Therapy Designation to idarucizumab in June 2014. The first study in humans with idarucizumab, the results of which the company presented in 2013, showed complete and sustained reversal of the anticoagulation effects of Pradaxa. The placebo-controlled study showed no clinically relevant side effects, no pro-thrombotic effects, and no return of anticoagulant activity.

RE-VERSE AD Trial

The RE-VERSE AD trial is titled, “Reversal of Dabigatran Anticoagulant Effect With Idarucizumab.” Investigators intend to study idarucizumab in rare, clinical settings involving patients treated with Pradaxa for a life-threatening bleeding event. Boehringer Ingelheim believes that recruiting may take some time because according to the RE-LY trial, life-threatening bleeding events are rare. July 2017 is the estimated primary completion date of the trial, and April 2017 will be the final data collection date for the primary outcome measure.

In the new Phase 3 trial, the company has set the primary outcome measure as the maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of dTT or ECT at any time point from the end of the first infusion up to 4 hours after the last infusion. Secondary measures include the reversal of Activated Partial Thromboplastin Time (aPTT), reversal of Thrombin Time (TT), and the duration of reversal.

Pradaxa

Pradaxa is a Boehringer Ingelheim product in a class of new oral anticoagulants. The FDA approved it in 2010 to prevent stroke in patients with atrial fibrillation and in 2014 for the treatment of deep venous thrombosis and pulmonary embolism. As Pradaxa is in a new class of drugs, antidotes are necessary to reverse its effects in severely bleeding patients.