Perioperative Management With Efanesoctocog Alfa in Patients With Haemophilia A in the Phase 3 XTEND-1 and XTEND-Kids Studies.

Abstract

Introduction: The Phase 3 studies, XTEND-1 (NCT04161495) and XTEND-Kids (NCT04759131), showed once-weekly efanesoctocog alfa provided high-sustained factor VIII (FVIII) activity levels that translated into highly effective bleed prevention in patients with severe haemophilia A.

Aim: This analysis evaluated the efficacy and safety of efanesoctocog alfa for perioperative management during XTEND-1 and XTEND-Kids.

Methods: Patients undergoing major or minor surgery were to receive a single preoperative 50 IU/kg dose, with additional 30 or 50 IU/kg doses every 2-3 days as needed following major surgery. Outcomes assessed included FVIII activity levels, number and dose of efanesoctocog alfa injections, surgeon's/investigator's assessment of haemostatic response, total factor consumption, estimated blood loss, number and type of blood transfusions, and safety.

Results: In XTEND-1, 11 adults/adolescents underwent 12 evaluable major surgeries (6 orthopaedic). Eleven surgeries had one preoperative dose (median [range]: 49.9 [13-52] IU/kg); one had no preoperative dose. Median (range) total consumption from Day -1 to 14 was 163.3 (45-361) IU/kg. In XTEND-Kids, two children underwent major surgery with a single preoperative loading dose (60.4 and 61.9 IU/kg). Across trials, 15 adults/adolescents underwent 18 minor surgeries and 8 children underwent 9 minor surgeries, with a single preoperative dose or no preoperative dose (5 surgeries in adults/adolescents). Haemostatic response was rated excellent for all surgeries. No surgeries required blood transfusion. No safety concerns or inhibitor development was reported.

Conclusion: Efanesoctocog alfa provided highly effective perioperative protection in patients with severe haemophilia A.

Trial registration: XTEND-1: NCT04161495 https://clinicaltrials.gov/study/NCT04161495; XTEND-Kids: NCT04759131 https://clinicaltrials.gov/study/NCT04759131.