PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors

Authors: Escobar, M; Luck, J; Averianov, Y; Ducore, J; Fernández, MFL; Giermasz, A; Hart, DP.; Journeycake, J; Kessler, C; Leissinger, C; Mahlangu, J; Martinez, LVl; Miesbach, W; Mitha, IH; Quon, D; Reding, MT.; Schved, J-F; Stasyshyn, O; Vilchevska, KV.; Wang, M; Windyga, J; Alexander, WA; Al-Sabbagh, A; Bonzo, D; Mitchell, IS.; Wilkinson, TA.; Hermans, C.

Affiliations: Gulf States Hemophilia and Thrombophilia Center, Houston, Texas, USA ; Orthopaedic Hemophilia Treatment Center, Los Angeles, California, USA ; City Research and Development Center for Diagnostics and Treatment of Patients with Abnormal Hemostasis, Kyiv, Ukraine ; Hematology/Oncology Clinic, University of California at Davis, Sacramento, California, USA ; Hemostasis and Thrombosis Unit, Teresa Herrera Hospital, A Coruña, Spain ; Division of Hematology/Oncology, University of California at Davis, Sacramento, California, USA ; The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, QMUL, London, UK ; Oklahoma Center for Bleeding and Clotting Disorders, Oklahoma City, Oklahoma, USA ; Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA ; Section of Hematology/Oncology, Tulane University School of Medicine, New Orleans, Louisiana, USA ; Hemophilia Comprehensive Care Center, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa ; Dr. José Eleuterio González Monterrey University Hospital, Monterrey, Nuevo León, México ; Goethe University Hospital, Frankfurt, Germany ; Lakeview Hospital, Benoni, Gauteng, South Africa ; Center for Bleeding and Clotting Disorders, University of Minnesota Medical Center, Minneapolis, Minnesota, USA ; Haemophilia Treatment Centre, University Hospital Montpellier, Montpellier, France ; Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine ; National Specialized Children’s Hospital Okhmatdyt, Kyiv, Ukraine ; 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 ; Aoede Associates, Athens, Texas, USA ; LFB-USA, Inc., Framingham, Massachusetts, USA

Publication: Haemophilia October 2021

ABSTRACT: INTRODUCTION Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses. AIM To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3. METHODS Subjects were administered 200 μg/kg (major procedures) or 75 μg/kg eptacog beta (minor procedures) immediately prior to the initial surgical incision; subsequent 75 μg/kg doses were administered to achieve postoperative haemostasis and wound healing. Efficacy was assessed on a 4-point haemostatic scale during the intra- and postoperative periods. Anti-drug antibodies, thrombotic events and changes in clinical/laboratory parameters were monitored throughout the perioperative period. RESULTS Twelve subjects underwent six major and six minor procedures. The primary efficacy endpoint success proportion was 100% (95% CI: 47.8%–100%) for minor procedures and 66.7% (95% CI: 22.3%–95.7%) for major procedures; 81.8% (95% CI: 48.2%–97.7%) of the procedures were considered successful using eptacog beta. There was one death due to bleeding from a nonsurgical site; this was assessed as unlikely related to eptacog beta. No thrombotic events or anti-eptacog beta antibodies were reported. CONCLUSION Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI.