FDA panel unanimously recommends approval for dabigatran

The FDA’s Cardiovascular and Renal Drugs Advisory Committee has voted 9 to 0 for approval of the investigational anticoagulant dabigatran, according to a press release. The panel also unanimously agreed that dabigatran, which is intended to prevent stroke and systemic embolism in patients with atrial fibrillation, is at least as effective as warfarin.

Dabigatran etexilate (Boehringer Ingelheim) is currently approved in Europe under the name Pradaxa and Canada under the name Pradax for venous-thromboembolism prophylaxis during hip- or knee-replacement surgery.

RE-LY trial

The vote follows a positive review issued by the FDA, which recommended that the 150-mg dose of dabigatran be approved. The review, however, also recommended against approval of the 110-mg dose.

The panel based its decision on the results of the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial. The study involved 18,113 patients across 951 sites who were randomly assigned to receive 110 mg or 150 mg of dabigatran twice daily compared with a warfarin dose adjusted to INR 2.0 to 3.0.

Data indicated that both doses of dabigatran demonstrated noninferiority to warfarin (P<.001). The 150-mg dose also appeared superior to warfarin, with a RR of 0.66 (95% CI, 0.53-0.82), but the FDA review stipulated that Boehringer Ingelheim cannot claim the drug’s superiority to warfarin upon approval.

Bleeding events

Major bleeding, the only serious adverse event, was reported in 2.75% of patients taking the low dose and in 3.36% of patients taking the high dose. Rates of life-threatening bleeding, intracranial bleeding and major or minor bleeding, however, were higher in patients receiving warfarin.

In a post hoc analysis of the RE-LY trial results funded by Boehringer Ingelheim, researchers said the benefits of dabigatran persisted, even as treatment centers’ international normalized ratio (INR) control varied.

“The benefits of 150-mg dabigatran at reducing stroke, 110-mg dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding vs. warfarin were consistent irrespective of centers’ quality of INR control,” they wrote.

The researchers said, however, that dabigatran’s positive effects on vascular and non-hemorrhagic events and mortality improved with better INR control.

An addendum to the FDA review also outlined concerns about an unexplained increase in rates of MI among patients in the dabigatran arm compared with those in the warfarin arm of the RE-LY trial. The reviewer recommended including this potential adverse event on the drug’s label until further information is available.

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