The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors

• Type of Material: Article
• Authors: Robert Sidonio Jr, Emory University; Miguel Escobar, Gulf States Hemophilia & Thrombophilia Ctr; Giancarlo Castaman, Careggi University Hospital; Santiago B Boix, University of Valencia; Michael Callaghan, Central Michigan University; Philippe de Moerloose, University of Geneva; Jonathan Ducore, University of California Davis; Cédric Hermans, Université Catholique de Louvain; Janna Journeycake, Oklahoma Bleeding & Clotting Disorders Ctr atOU H; Cindy Leissinger, Tulane University; James Luck, Orthopaedic Hemophilia Treatment Center; Johnny Mahlangu, University of Witwatersrand; Wolfgang Miesbach, Goethe University Hospital; Ismail Haroon Mitha, Lakeview Hospital; Claude Négrier, Edouard Herriot University Hospital; Doris Quon, Orthopaedic Hemophilia Treatment Center; Michael Recht, Amer Thrombosis & Hemostasis Network; Jean François Schved, University Hospital Montpellier; Amy D Shapiro, Indiana Hemophilia and Thrombosis Center; Robert Sidonio, Emory University; Alok Srivastava, Christian Medical College, Vellore Tamil Nadu, India; Oleksandra Stasyshyn, Institute of Blood Pathology & Transfusion Medicine; Kateryna V Vilchevska, National Specialized Children's Hospital Okhmatdyt; Michael Wang, University of Colorado, Aurora; Guy Young, Children's Hospital Los Angeles; Allan W Alexander, Aoede Associates; Ahmad Al-Sabbagh, LFB‐USA, Inc.; Daniel Bonzo, LFB‐USA, Inc.; Christopher Macie, HEMA Biol LLC; Thomas A Wilkinson, GLOVAL LLC; Craig Kessler, Georgetown University
• Language: English
• Date: 2021-10-11
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/hae.14419
• Title of Journal or Parent Work: HAEMOPHILIA
• Volume: 27
• Issue: 6
• Start Page: 921
• End Page: 931
• Keywords: MULTICENTER; RECEPTOR; PERSEPT; recombinant FVIIa; TRIAL; NOVOSEVEN; Life Sciences & Biomedicine; Science & Technology; EFFICACY; RFVIIA; inhibitors; CONGENITAL HEMOPHILIA; Hematology; SEVENFACT; haemophilia; eptacog beta; FACTOR-IX; safety; UPDATE; RECOMBINANT FACTOR-VIIA
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Introduction: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date. Aim: To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care. Methods: Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 μg/kg EB initially followed by 75 μg/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 μg/kg (minor procedures) or 200 μg/kg EB (major surgeries) with subsequent 75 μg/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses. Results: Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee. Conclusion: Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use.