While current guidelines for treating patients with hemophilia A or B recommend intravenous factor VIII or IX concentrates, many patients develop antibodies to these drugs (i.e., inhibitors) and/or repeated venipuncture becomes a severe burden. Concizumab, a monoclonal antibody that is administered subcutaneously, is under investigation as an alternative treatment for all types of hemophilia. Concizumab works by stabilizing factor Xa production normalizing thrombin generation. New data from the explorer7 open-label, prospective phase 3 clinical trial offers promising data on the safety and efficacy of daily and subcutaneous concizumab in patients who have hemophilia A or B and inhibitors. During the trial, 133 patients (>12 years old) who have hemophilia A or B with inhibitors were randomized 1:2 to receive no prophylaxis for at least 24 weeks (N=19) or concizumab daily for at least 32 weeks (N=33); in addition, 81 patients were non-randomly assigned to receive concizumab for at least 24 weeks. Patients who did not receive prophylaxis had a mean annualized bleeding rate of 11.8 episodes compared to 1.7 episodes (rate ratio, 0.14 [95% CI, 0.07 to 0.29]; p<0.001). While the study was paused due to nonfatal thromboembolic events and an altered dose regimen was implemented partway through the study, no thromboembolic events were reported after the study was restarted. This trial confirmed superiority of concizumab compared to no prophylaxis for hemophilia patients with inhibitors.
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