FDA approves Pradaxa (dabigatran etexilate mesylate) for deep venous thrombosis and pulmonary embolism- Boehringer Ingelheim

The FDA approved Pradaxa (dabigatran etexilate mesylate), from Boehringer Ingelheim, for the prophylaxis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have undergone hip replacement surgery. This represents the fourth FDA-approved indication for Pradaxa in five years.

The FDA approval is based on the results of two randomized, double-blind, phase III trials in patients undergoing total hip replacement, RE-NOVATE and RE-NOVATE II. In RE-NOVATE, 3,494 patients were randomized to three groups receiving prophylactic treatment with one of two doses of Pradaxa (220 mg or 150 mg) once daily or enoxaparin 40 mg once daily for 28 to 35 days. The first PRADAXA group was given a dose of 110 mg on the day of surgery and 220 mg daily thereafter; the second Pradaxa group received a dose of 75 mg on the day of surgery and 150 mg daily thereafter. In RE-NOVATE II, 2,055 patients were randomly assigned prophylactic treatment for 28 to 35 days with Pradaxa 220 mg once daily or enoxaparin 40 mg once daily. Patients receiving Pradaxa were treated with a dose of 110 mg on the day of surgery and 220 mg daily thereafter. The results of RE-NOVATE showed patients taking Pradaxa 220 mg had a lower composite total of venous thromboembolism (VTE, which comprises DVT and PE) and all-cause death (6.0 percent) than those on enoxaparin 40 mg (6.7 percent). In RE-NOVATE II, the composite total of VTE and all-cause death occurred in 7.7 percent of patients in the Pradaxa group vs. 8.8 percent of patients in the enoxaparin group.

There were higher rates of major bleeding in RE-NOVATE (2.0%, 1.6%) and RE-NOVATE II (1.4%, 0.9%) with 220 mg vs. enoxaparin. In the two studies, the rate of major gastrointestinal bleeds in patients receiving Pradaxa and enoxaparin was the same (0.1%) and for any gastrointestinal bleeds was 1.4% for Pradaxa and 0.9% for enoxaparin. The most common adverse events in both studies were gastrointestinal disorders. Incidence was the same across the Pradaxa and enoxaparin treatment groups (39.5%).

Comment:Pradaxa is facing strong competition, including Eliquis (apixaban) from BMS/Pfizer, while other treatments available to treat DVT and/or PE include: warfarin, heparin,and Xarelto (rivaroxaban) from Bayer/Johnson & Johnson.