New RE-VERSE AD™ Analyses Provide Additional Insights on Impact of Idarucizumab (Praxbind®) in Pradaxa® Patients with Gastrointestinal Bleeding or Needing Emergency Surgery

Ridgefield, Conn., November 13, 2017 – Boehringer Ingelheim today announced results from two new analyses of the phase III RE-VERSE AD™ study, which evaluated the safety and efficacy of idarucizumab, marketed in the U.S. as Praxbind®, in reversing the anticoagulant effect of Pradaxa® (dabigatran etexilate mesylate) in patients in diverse emergency situations, including those with acute bleeding or requiring an urgent surgery or procedure, such as an orthopedic, vascular or abdominal procedure. The analyses, presented today at the American Heart Association (AHA) Scientific Sessions 2017 in Anaheim, California, provide further insights on the use of idarucizumab in patients with gastrointestinal (GI) bleeding and in those with a need for urgent surgery or intervention.

“The RE-VERSE AD study has demonstrated that idarucizumab can reverse the anticoagulant effect of dabigatran within minutes, allowing physicians to quickly initiate emergency interventions for patients who need urgent surgery or are experiencing uncontrollable bleeding,” said Charles Pollack, M.D., lead investigator of RE-VERSE AD, Professor of Emergency Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, USA. “These new analyses further reinforce the potential for idarucizumab to enhance care for people living with atrial fibrillation.”

One of the subanalyses focused on patients with GI bleeding, the most common type of bleeding event among patients who were enrolled in the study due to acute bleeding. Of the 137 patients enrolled with a GI bleed, complete reversal of the anticoagulant effect of Pradaxa was observed in more than 95 percent of patients. The median time to cessation of bleeding post-idarucizumab administration was less than 3 hours when the location of the GI bleed was known and 6.4 hours when the location was unknown.

Mortality and thromboembolic event rates for patients with a GI bleed were consistent with the overall findings of RE-VERSE AD. In the subanalysis, as presented in the abstract, at 90 days, there were low thromboembolic event rates of 5.1 percent in patients with a GI bleed, compared to 6.3 percent in non-GI bleed patients. Mortality in the first 5 days following administration was 6 percent in patients with a GI bleed, compared to 9 percent in non-GI bleed patients. At 90 days, mortality rates were 16 percent and 23 percent, respectively.

Also presented at AHA were updated results assessing periprocedural bleeding in patients requiring an urgent procedure, such as an emergency surgery. Idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in approximately 98 percent of patients based on dTT. The median time between administration of idarucizumab and start of surgery was 1.7 hours for patients requiring abdominal procedures, 1.9 hours for orthopedic procedures, 1.4 hours for vascular procedures, 1.3 hours for drainage procedures and 1.2 hours for catheter procedures. Among these patients, periprocedural bleeding was assessed as normal in more than 92 percent of patients, across all surgery types. Among patients needing emergency surgery, none were assessed as experiencing periprocedural bleeding that was severely abnormal. RE-VERSE AD is the only study to investigate anticoagulation reversal among patients requiring surgery.

“Boehringer Ingelheim is proud to provide additional insights for patients and healthcare providers through new analyses of the impact of idarucizumab, which is widely available to patients nationwide through hospital pharmacies,” said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “In addition to RE-VERSE AD – the largest study investigating a NOAC reversal agent in real-world emergency settings – we continue to study idarucizumab through the RE-VECTO™ program, which evaluates usage patterns in the clinical practice setting.”

About RE-VERSE AD™

RE-VERSE AD (NCT02104947(link is external)) is a phase III global study of patients taking dabigatran who require urgent procedures or have uncontrolled bleeding. The final analysis from RE-VERSE AD included data from patients requiring urgent procedures/emergency surgery, e.g. surgery for an open fracture after a fall, or patients with either uncontrolled or life-threatening bleeding complications, e.g. intracranial hemorrhage or severe trauma after a car accident. The primary endpoint, the degree of reversal of the anticoagulant effect of dabigatran (Pradaxa) achieved by idarucizumab within four hours, was measured by dTT and ECT.

The study, which began in May 2014, is the largest study to investigate a reversal agent for a novel oral anticoagulant (NOAC) in real-world emergency settings. It enrolled a total of 503 patients at 173 sites in 39 countries, which were included in one of two groups:

• Group A: 301 patients (60 percent) presenting with uncontrolled or life-threatening bleeding (e.g. gastrointestinal [GI] and intracranial [ICH] bleeds)
• Group B: 202 patients (40 percent) requiring an invasive procedure or an emergency surgery or intervention (e.g. because of a hip fracture)