Eptacog beta efficacy and safety in the treatment and control of bleeding in paediatric subjects (<12 years) with haemophilia A or B with inhibitors

Authors: Pipe, SW; Hermans, C; Chitlur, M; Carcao, M; Castaman, G; Davis, JA; Ducore, J; Dunn, AL; Escobar, M; Journeycake, J; Khan, O; Mahlangu, J; Meeks, SL; Mitha, IH; Négrier, C; Nowak-Göttl, U; Recht, M; Chrisentery-Singleton, T; Stasyshyn, O; Vilchevska, KV; Martinez, LV; Wang, M; Windyga, J; Young, G; Alexander, WA; Bonzo, D; Macie, C; Mitchell, IS; Sauty, E; Wilkinson, TA; Shapiro, AD

Affiliations: University of Michigan, Ann Arbor, Michigan, USA. Cliniques Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. Children’s Hospital of Michigan, Central Michigan University, Detroit, Michigan, USA. The Hospital for Sick Children, Toronto, Ontario, Canada. Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy. Pediatric Hemophilia Treatment Center, University of Miami, Miami, Florida, USA. Hematology/Oncology Clinic, University of California at Davis, Sacramento, California, USA. Nationwide Children’s Hospital, Department of Pediatrics at The Ohio State University College of Medicine, Columbus, Ohio, USA. University of Texas Health Science Center at Houston, Houston, Texas, USA. Oklahoma Center for Bleeding and Clotting Disorders at OU Health, Oklahoma City, Oklahoma, USA. Hemophilia Comprehensive Care Center, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa. Emory University and Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Atlanta, Georgia, USA. Lakeview Hospital, Benoni, Gauteng, South Africa. Edouard Herriot University Hospital, Lyon, France. Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel, Germany. American Thrombosis and Hemostasis Network, Rochester, New York, USA. Oregon Health & Science University, Portland, Oregon, USA. Louisiana Center for Advanced Medicine, Slidell, Louisiana, USA. Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine. National Specialized Children’s Hospital Okhmatdyt, Kyiv, Ukraine. Dr. José Eleuterio González Monterrey University Hospital, Monterrey, Nuevo León, México. Hemophilia and Thrombosis Center, University of Colorado, Aurora, Colorado, USA. Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. Children’s Hospital Los Angeles, Los Angeles, California, USA. Keck School of Medicine, University of Southern California, Los Angeles, California, USA. Aoede Associates, Athens, Texas, USA. LFB-USA, Inc., Framingham, Massachusetts, USA. HEMA Biologics, LLC, Louisville, Kentucky, USA. LFB, Laboratoire français du fractionnement et des biotechnologies, Les Ulis, France. GLOVAL LLC, Broomfield, Colorado, USA. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA.

Publication: Haemophilia; 2022; 28. 548–556

Abstract: INTRODUCTION: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. AIM: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children <12 years of age with haemophilia A or B with inhibitors. METHODS: Using a randomized crossover design, subjects received initial doses of 75 or 225 μg/kg eptacog beta followed by 75 μg/kg dosing at predefined intervals (as determined by clinical response) to treat bleeding episodes (BEs). Treatment success criteria included a haemostasis evaluation of ‘excellent’ or ‘good’ without use of additional eptacog beta, alternative haemostatic agent or blood product, and no increase in pain following the first ‘excellent’ or ‘good’ assessment. RESULTS: Treatment success proportions in 25 subjects (1-11 years) who experienced 546 mild or moderate BEs were 65% in the 75 μg/kg initial dose regimen (IDR) and 60% in the 225 μg/kg IDR 12 h following initial eptacog beta infusion. By 24 h, the treatment success proportions were 97% for the 75 μg/kg IDR and 98% for the 225 μg/kg IDR. No thrombotic events, allergic reactions, neutralizing antibodies or treatment-related adverse events were reported. CONCLUSION: Both 75 and 225 μg/kg eptacog beta IDRs provided safe and effective treatment and control of bleeding in children <12 years of age.