• Lynn Malec, Flora Peyvandi, ChanAnthony K CAKCFrom Versiti Blood Research Institute, and the Division of Hematology and Oncology, Departments of Medicine and Pediatrics, Medical College of Wisconsin - both in Milwaukee (L.M.); IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bi, Christoph Königs, Bulent Zulfikar, Huixing Yuan, Mindy Simpson, Maria Teresa Álvarez Román, Manuel Carcao, Janice M Staber, Amy L Dunn, Sheng-Chieh Chou, Roseline d'Oiron, Manuela Albisetti, Marek Demissie, Elena Santagostino, Abhimanyu Yarramaneni, Nancy Wong, Lydia Abad-Franch, Sriya Gunawardena, Karin Fijnvandraat, and XTEND-Kids Trial Group.
• From Versiti Blood Research Institute, and the Division of Hematology and Oncology, Departments of Medicine and Pediatrics, Medical College of Wisconsin - both in Milwaukee (L.M.); IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, and Università degli Studi di Milano, Department of Pathophysiology and Transplantation - both in Milan (F.P.); McMaster Children's Hospital, McMaster University, Hamilton, ON (A.K.C.C.), and the Division of Hematology-Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto (M.C.) - both in Canada; Goethe University Frankfurt, University Hospital, Department of Pediatrics and Adolescent Medicine, Frankfurt, Germany (C.K.); the Department of Pediatric Hematology, Istanbul University Oncology Institute, Inherited Bleeding Disorders, Istanbul, Turkey (B.Z.); Sanofi, Cambridge, MA (H.Y., M.D.); Rush University Medical Center, Rush Hemophilia and Thrombophilia Center, Chicago (M.S.); Hospital Universitario La Paz, Autonoma University of Madrid, IdiPAZ, Madrid (M.T.Á.R.); University of Iowa Stead Family Children's Hospital, Carver College of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant, Iowa City (J.M.S.); the Division of Hematology, Oncology, and Blood and Marrow Transplant at Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.L.D.); the Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (S.-C.C.); Centre de Référence de l'Hémophilie et des Maladies Hémorragiques Constitutionnelles and Hémostase Inflammation Thrombose, Unité Mixte de Recherche S1176, INSERM, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, Le Kremlin-Bicêtre, France (R.O.); University Children's Hospital, Zurich (M.A.), and Sobi, Basel (E.S., L.A.-F.) - both in Switzerland; Sanofi, Bridgewater, NJ (A.Y., N.W., S.G.); and Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Pediatric Hematology, Amsterdam (K.F.).
• N. Engl. J. Med. 2024 Jul 18; 391 (3): 235246235-246.

BackgroundOnce-weekly efanesoctocog alfa provides high sustained factor VIII activity with superior bleeding prevention as compared with prestudy factor VIII prophylaxis in previously treated patients 12 years of age or older with severe hemophilia A. Data on outcomes of efanesoctocog alfa treatment in children younger than 12 years of age with severe hemophilia A are limited.MethodsWe conducted a phase 3, open-label study involving previously treated patients younger than 12 years of age with severe hemophilia A. Patients received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. The primary end point was the occurrence of factor VIII inhibitors (neutralizing antibodies against factor VIII). Secondary end points included annualized rates of treated bleeding episodes, bleeding treatment, safety, and pharmacokinetics.ResultsA total of 74 male patients were enrolled (38 with an age of <6 years and 36 with an age of 6 to <12 years). No factor VIII inhibitors developed. Most adverse events were nonserious. No serious adverse events that were assessed by the investigator as being related to efanesoctocog alfa were reported. In the 73 patients treated according to the protocol, the median and model-based mean annualized bleeding rates were 0.00 (interquartile range, 0.00 to 1.02) and 0.61 (95% confidence interval, 0.42 to 0.90), respectively. A total of 47 patients (64%) had no treated bleeding episodes, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints. A total of 41 of 43 bleeding episodes (95%) resolved with one injection of efanesoctocog alfa. Mean factor VIII activity at steady state was more than 40 IU per deciliter for 3 days and more than 10 IU per deciliter for almost 7 days after dose administration. The geometric mean terminal half-life was 40.0 hours.ConclusionsIn children with severe hemophilia A, once-weekly prophylaxis with efanesoctocog alfa provided high sustained factor VIII activity in the normal to near-normal range (>40 IU per deciliter) for 3 days and more than 10 IU per deciliter for almost 7 days after administration, leading to effective bleeding prevention. Efanesoctocog alfa was associated with mainly nonserious adverse events. (Funded by Sanofi and Sobi; XTEND-Kids ClinicalTrials.gov number, NCT04759131.).Copyright © 2024 Massachusetts Medical Society.

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