September 8th, 2011

FDA Advisory Panel Gives Yellow Light to Rivaroxaban

The FDA Cardiovascular and Renal Drugs Advisory Committee voted 9-2 (with 1 abstention) in support of rivaroxaban (Xarelto, Johnson & Johnson) for stroke prevention in patients with atrial fibrillation, but the vote did not represent a ringing endorsement of the drug. The committee wrestled throughout the day with the numerous concerns raised by FDA reviewers, who had recommended that the drug be rejected. The committee left three key issues for the FDA to resolve if it approves the drug:

  • Although rivaroxaban was noninferior to warfarin in the pivotal ROCKET trial, warfarin was not used as skillfully in ROCKET as in RE-LY and other recent trials, thereby making it difficult to assess the true efficacy of rivaroxaban.
  • Because of a high number of events observed in patients when they discontinued use of rivaroxaban, there is no firm guidance for how to transition patients to warfarin or other drugs when rivaroxaban is discontinued.
  • The optimal dose of rivaroxaban is still unclear. Many on the committee thought rivaroxaban might perform better as a twice-a-day drug.

4 Responses to “FDA Advisory Panel Gives Yellow Light to Rivaroxaban”

  1. Judith Andersen, AB, MD says:

    It is really not clear why the FDA advisory panel, ( and FDA reviewers, who seem to have had it in for this drug from the outset — witness that ridiciulous discussion last year with regard to statistical miscalculation, liver dysfunction — Hy’s rules– and dosing during the discussion regarding orthopedic VTE prophylaxis) with supporting data at least as good as that for dabigatran, is still dragging its theoretical feet. The warfarin in-range results in ROCKET are at least as good as those achieved in most dedicated warfarin anticoagulation clinics, and likely far better than those achieved in individual cardiology practices, and issues related to transition to other drugs (what other drugs and why would one transition a patient from rivaroxaban to warfarin or another anticoagulant, except for non-approval by an insurance company ? Side effects — compared to warfarin ???) were barely mentioned in the discussion with regard to dabigatran. One wonders whether this panel is really capable of objective evaluation of agents that compete with an established treatment paradigm — even when their use is supported by data from some of the largest randomized clinic trials ever performed in this therapeutic arena.

    Competing interests pertaining specifically to this post, comment, or both:
    None. I supervise a large urban anticoagulation clinic and have a vested interest in good clinical outcomes and In-range warfarin use, not any specific drug — and am very familiar with the less than perfect results achieved with every-day best practice warfarin anticoagulation management. I welcomed the approval of dabigatran for non-valvular a fib and jeered at the foot-dragging by the FDA in approval of rivaroxaban for VTE prophylaxis in orthopedic surgery , where timely approval would have meant that literally thousands of patients would not have experienced perioperative venous thrombosis and pulmonary embolism from established orthopedic “worst practice” in the year that the FDA postponed its approval. Wimps! Patients who experienced VTE and insurance companies who were required to pay for hospital admissions for VTE following orthopedic surgery during this period should have something to say about this.

  2. David Powell , MD, FACC says:

    RE-LY showed superiority in the primary outcpme. The FDA did not grant a superiority claim, as those with high TTRs likely have no benedit with dabi for the primary endpoint and this is a single study. So…ROCKET shows noninferiority with lesser INR control. How confident are we that rivaroxaban is noninferior for those with higher TTRs? The statistics are essential. The FDA has much more information and data…perhaps available at their website. I learned a lot from looking at the FDA documents on dabigatran at the site. It may be unfair to cast judgement on FDA opinions without seeing all the data.

    Competing interests pertaining specifically to this post, comment, or both:
    speaker for BI…but optimistic re apixaban

  3. Joel Wolkowicz, MDCM says:

    This is the same FDA that approved a dose of dabigatran (75 mg BID) that was never tested, and declined to approve 110 mg BID even though it was as effective, with less bleeding, than warfarin. I have a hard time assuming that the FDA should be trusted based on data not available to us. Criticizing the “low” TTR is hypocritical – do they think this number is higher when patients are followed by busy PCP’s?

    Competing interests pertaining specifically to this post, comment, or both:
    None. Just trying to take care of patients.

  4. Joseph Wildman, MD says:

    One has to suspect-yet again-some peculiar FDA bias against rivaroxaban-and/or in favor of dabigatran. Where do we find full disclosure of potential conflicts of interest in the FDA or its advisory panels? How is it that rivaroxaban was approvable more than 2 years ago in the rest of the world–but not here? The quibble about warfarin management in ROCKET really raises a red flag in my mind.