Major Surgical Outcomes with Efanesoctocog Alfa: 4 Years’ Experience in the XTEND Clinical Program

Introduction Efanesoctocog alfa is a first-in-class high sustained factor VIII replacement therapy that overcomes the von Willebrand factor-imposed half-life ceiling. Once-weekly treatment (50 IU/kg) demonstrated high efficacy and was well tolerated in patients with severe hemophilia A (XTEND-1/NCT04161495; XTEND-Kids/NCT04759131). Participants completing the XTEND-1 or XTEND-Kids studies could enter XTEND-ed (NCT04644575).Here, wereport major surgical data from parent studies’ baselines through XTEND-ed second interim analysis (datacut: February 22, 2024). Method Participants provided informed consent; the study was approved by applicable review boards. Participants from the XTEND-1 and XTEND-Kids studies and those newly initiating efanesoctocog alfa prophylaxis were included. Participants received 50 IU/kg preoperatively (day of surgery) per-protocol; 30 or 50 IU/kg was administered every 2–3 days postoperatively as needed. Short-term perioperative thromboembolic prophylaxis was allowed. Results Forty surgeries (30 orthopedic, 10 nonorthopedic) were performed in 32 males; [ Fig. 1 ]. For orthopedic surgeries, 2/30 (6.7%) did not require a preoperative dose (Day -1,0). Median (range) total dose to maintain hemostasis (Day -1,0) was 50.0 (12.7–84.7) IU/kg, number of injections during perioperative period (Day -1–14) was 5.0 (2–9), estimated intraoperative blood loss was 140 (0–1000) mL; 2 required transfusions. Median (Q1,Q3) time from surgery to return to prophylaxis was 15 (10,29) days. Hemostatic response was excellent/good in 93.3% cases. One preoperative dose maintained hemostasis in all nonorthopedic surgeries. Median (range) total dose was 51.7 (48.4–60.4) IU/kg, number of injections (Day -1–14) was 3.0 (2–7). Median (Q1,Q3) time to return to prophylaxis was 9 (6,14) days. Hemostatic response was excellent/good in all cases. Efanesoctocog alfa was well tolerated. Fig. 1