• Johannes Oldenburg, Johnny N Mahlangu, Benjamin Kim, Christophe Schmitt, Michael U Callaghan, Guy Young, Elena Santagostino, Rebecca Kruse-Jarres, Claude Negrier, Craig Kessler, Nancy Valente, Elina Asikanius, Gallia G Levy, Jerzy Windyga, and Midori Shima.
• From Universitätsklinikum Bonn, Bonn, Germany (J.O.); the Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, Johannesburg (J.N.M.); Genentech, South San Francisco (B.K., N.V., G.G.L.), and Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles (G.Y.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (C.S., E.A.); Children's Hospital of Michigan, Detroit (M.U.C.); the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Foundation, Ospedale Maggiore Policlinico, Milan (E.S.); Bloodworks Northwest, Seattle (R.K.-J.); Louis Pradel Cardiology Hospital, University Claude Bernard, Lyon, France (C.N.); Georgetown University Medical Center, Washington, DC (C.K.); the Department of Disorders of Hemostasis and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland (J.W.); and the Department of Pediatrics, Nara Medical University, Kashihara, Japan (M.S.).
• N. Engl. J. Med. 2017 Aug 31; 377 (9): 809-818.

BackgroundEmicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors.MethodsWe enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C.ResultsA total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (P<0.001). A total of 22 participants in group A (63%) had zero bleeding events, as compared with 1 participant (6%) in group B. Among 24 participants in group C who had participated in a noninterventional study, emicizumab prophylaxis resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing-agent prophylaxis (P<0.001). Overall, 198 adverse events were reported in 103 participants receiving emicizumab prophylaxis; the most frequent events were injection-site reactions (in 15% of participants). Thrombotic microangiopathy and thrombosis were reported in 2 participants each (in the primary analysis) who had received multiple infusions of activated prothrombin complex concentrate for breakthrough bleeding. No antidrug antibodies were detected.ConclusionsEmicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis among participants with hemophilia A with inhibitors. (Funded by F. Hoffmann-La Roche and Chugai Pharmaceutical; HAVEN 1 ClinicalTrials.gov number, NCT02622321 .).

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