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

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 27; no. 6; pp. 911 - 920
• Main Authors: Escobar, Miguel, Luck, James, Averianov, Yevhenii, Ducore, Jonathan, Fernández, Maria Fernanda López, Giermasz, Adam, Hart, Daniel P., Journeycake, Janna, Kessler, Craig, Leissinger, Cindy, Mahlangu, Johnny, Martinez, Laura Villarreal, Miesbach, Wolfgang, Mitha, Ismail Haroon, Quon, Doris, Reding, Mark T., Schved, Jean‐François, Stasyshyn, Oleksandra, Vilchevska, Kateryna V., Wang, Michael, Windyga, Jerzy, Alexander, W. Allan, Al‐Sabbagh, Ahmad, Bonzo, Daniel, Mitchell, Ian S., Wilkinson, Thomas A., Hermans, Cédric
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2021; John Wiley and Sons Inc
• Subjects: Antibodies; Antiplatelet therapy; Clinical trials; Coagulation factor VIIa; eptacog beta; Factor VIIa; haemophilia; Hemophilia; Hemophilia A - drug therapy; Hemostasis; Hemostatics - therapeutic use; Humans; inhibitors; Original; Perioperative Care; PERSEPT; recombinant FVIIa; Recombinant Proteins; SEVENFACT; surgery; Wound healing; inhibitors; recombinant FVIIa; PERSEPT; eptacog beta; haemophilia; SEVENFACT; surgery
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.14418

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.