SILVER SPRING, Md. – A Food and Drug Administration advisory panel on Sept. 20 unanimously voted to recommend that dabigatran, an orally administered direct thrombin inhibitor, be approved for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
The panel based the decision on the results of the Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) trial, a noninferiority, randomized international study of 18,113 patients with nonvalvular atrial fibrillation (AF) and at least one risk factor for stroke, which compared two blinded doses of dabigatran to open-label warfarin on the incidence of stroke and systemic embolism, the primary end point.
Both doses of dabigatran were considered noninferior to warfarin for preventing stroke and systemic embolism, and the 150 mg dose was more effective than warfarin and the 100 mg dose in preventing stroke and systemic embolism, according to the company, Boehringer Ingelheim Pharmaceuticals Inc. Both doses were associated with a reduction in hemorrhagic stroke and when compared to warfarin, the vascular death risk was reduced with the higher dose.
Compared to warfarin, the 150 mg dose was associated with a significantly increased risk of major GI bleeding, but also associated with a significant reduction in life-threatening and total bleeding. The 110 mg dose was also associated with a significant reduction in major, life-threatening, and total bleeding, when compared to warfarin. More patients on dabigatran had myocardial infarctions (1.4% and 1.5% among those on 110 mg and 150 mg, compared with 1.1% of those on warfarin).
The panel agreed that the study provided strong evidence that both dabigatran doses had been shown to be noninferior to warfarin therapy in the study, and several said they believed the 150 mg dose had been shown to be superior to warfarin.
Of the five cardiologists on the panel, three supported approval of the 150 mg dose only, because they were concerned that if both doses were available, clinicians might primarily prescribe the lower dose as the “default” dose because of fears over adverse events with the lower dose, and many patients would be deprived of a drug they considered more effective than warfarin.
Dabigatran was approved in 2008 in the European Union, Canada, Australia, Brazil and other countries for primary prevention of venous thromboembolic events in adults who have undergone elective be total hip replacement or total knee replacement surgery, according to Boehringer. It is marketed under the trade name Pradaxa, which will also be the trade name in the United States, if approved by the FDA.
The FDA’s decision is expected by Oct. 19. The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of disclosures related to the topic of the meeting, although occasionally, are granted waivers.