Boehringer Ingelheim Initiates U.S. Sites in First-Ever Global Phase III Trial of Investigational Antidote in Patients Taking PRADAXA®

• - RE-VERSE AD™ is being conducted in more than 35 countries with aim to enroll 250 patients
• Idarucizumab*, a humanized antibody fragment (Fab), is being investigated as a specific antidote for PRADAXA

RIDGEFIELD, Conn., Boehringer Ingelheim Pharmaceuticals, Inc. today announced the initiation of U.S. sites of the RE-VERSE AD™ trial (NCT02104947), a phase III global study investigating idarucizumab* in actual clinical settings where Pradaxa® (dabigatran etexilate mesylate) patients may require emergency intervention or experience an uncontrolled or life-threatening bleeding event. Idarucizumab is an investigational humanized antibody fragment (Fab) being studied as a specific antidote for PRADAXA. This is the first-ever trial to investigate an antidote in patients actively being treated with a newer oral anticoagulant.

"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," said Dr. Charles Pollack, Professor of Emergency Medicine at the Perelman School of Medicine at the University of Pennsylvania, Chairman of Emergency Medicine at Pennsylvania Hospital in Philadelphia and lead investigator of the patient study. "RE-VERSE AD will help further inform the effects of idarucizumab in real-world situations where the antidote could be a potential therapeutic option in very specific, and typically rare, clinical settings involving patients treated with PRADAXA."

Based on the low rates of life-threatening bleeding observed in the RE-LY® trial, and as seen in post-marketing safety data, Boehringer Ingelheim anticipates enrollment may take an extended period. As a result, RE-VERSE AD is being conducted in more than 35 countries and will aim to enroll a total of 250 patients.

"This trial is the next step in the development of idarucizumab, which began prior to regulatory approval of PRADAXA in 2010," said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "While PRADAXA's favorable risk-benefit profile has been well-established in clinical trials and reinforced through real-world analyses without an antidote, BI is committed to offering healthcare providers an additional therapeutic option to be considered should a patient require emergency intervention or if a patient experiences uncontrolled bleeding."

High-level data from the first study in healthy human volunteers, presented at the American Heart Association's (AHA) Scientific Sessions in November 2013, showed that intravenous administration of idarucizumab resulted in immediate, complete and sustained reversal of the anticoagulation effects of PRADAXA. In a placebo-controlled study, idarucizumab did not cause any clinically relevant side effects. No pro-thrombotic effect was observed after the administration of idarucizumab and no return of anticoagulant activity of PRADAXA was seen over time at adequate doses.

In June 2014, the U.S. Food and Drug Administration granted Breakthrough Therapy Designation to idarucizumab. Boehringer Ingelheim plans to present additional data analyses from healthy human volunteer trials at the upcoming AHA Scientific Sessions and American Society of Hematology Annual Meeting in November and December 2014.

Source: Boehringer Ingelheim Pharmaceuticals, Inc.