Perioperative Management with Efanesoctocog Alfa in Adults, Adolescents, and Children with Severe Hemophilia A in the Phase 3 XTEND Clinical Program

Introduction: Efanesoctocog alfa (formerly BIVV001) is a first-in-class high-sustained factor VIII replacement therapy that provides effective bleed prevention with once-weekly dosing (50 IU/kg) in previously treated patients with severe hemophilia A. Here, we evaluate efficacy and safety of efanesoctocog alfa for perioperative management in the Phase 3 XTEND clinical program.

Method: XTEND-1 (NCT04161495) and XTEND-Kids (NCT04759131) studies assessed safety and efficacy of efanesoctocog alfa in previously treated patients≥12 and<12 years old, respectively, with severe hemophilia A. Participants from each study could continue treatment in the XTEND-ed study (NCT04644575). Participants provided informed consent, and studies were approved by ethics committees. Participants undergoing surgery were to receive a pre-operative loading dose of efanesoctocog alfa 50 IU/kg. For major surgeries, post-operative doses of 30 or 50 IU/kg every 2–3 days were allowed. Surgery endpoints included dose, number of injections, hemostatic response, factor consumption, blood loss, and blood transfusions during the perioperative period. Interim data cut: January 17, 2023.

Results: Forty-one participants (<18 years, n=9;≥18 years, n=32) underwent 49 major surgeries ([Fig. 1]); 23 were orthopedic surgeries, with knee arthroplasty most common (n=12). All single 50 IU/kg pre-operative doses maintained hemostasis during major surgery. Median (range) number of doses per major surgery was 4.0 (1–7) during the perioperative period (Days−1 to 14). Hemostatic response was rated excellent for 43 surgeries and good for 5 surgeries. Median (range) blood loss was 20 (0–1000) mL during surgery (n=29); red blood cell transfusion was required for 1 total knee replacement. Of 32 minor surgeries ([Fig. 2]) among 28 participants, 27 were managed with 1 pre-operative dose and 5 with no pre-operative dose. Of those with an assessment (n=25), all hemostatic responses were rated excellent.

Fig. 1  Summary of outcomes during the perioperative period for major surgeries among participants from the XTEND-1, XTEND-Kids, and XTEND-ed studies

Fig. 2  Summary of outcomes during the perioperative periodfor minor surgeries among participants from the XTEND-1, XTEND-Kids, and XTEND-ed studies

Conclusion: Efanesoctocog alfa was effective and well tolerated for perioperative management in participants with severe hemophilia A.

Funded by Sanofi and Sobi.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025