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Clinical Trial
. 2025 May;31(3):391-400.
doi: 10.1111/hae.70017. Epub 2025 Mar 18.

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

Robert Klamroth  1 , Annette von Drygalski  2 , Cedric Hermans  3 , Young-Shil Park  4 , Anthony K C Chan  5 , Alphan Kupesiz  6 , María Teresa Alvarez-Román  7 , Lynn Malec  8   9 , Elena Santagostino  10 , Graham Neill  11 , Linda Bystrická  10 , Jennifer Dumont  12 , Lydia Abad-Franch  10 , Lila-Sabrina Fetita  13 , Liane Khoo  14
Affiliations
Clinical Trial

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

Robert Klamroth et al. Haemophilia. 2025 May.

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.

Keywords: BIVV001; adults; children; haematology; haemophilia; haemostasis; surgical procedures, operative.

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Conflict of interest statement

Robert Klamroth has received honoraria and/or been a member of advisory committees for Bayer, Biomarin, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Sobi, and Shire/Takeda. Annette von Drygalski has received fees from Biomarin, Bioverativ/Sanofi‐Genzyme, Novo Nordisk, Takeda, and Uniqure for participation in industry‐sponsored education events and advisory boards. She has received research funding from Bioverativ/Sanofi‐Genzyme and Pfizer. She is a co‐founder and a member of the board of directors of Hematherix Inc. She holds a patent for a superFactorVa, and she is the inventor and physician lead for the Joint Activity and Damage Examination (JADE) ultrasound measurement tool. JADE is copyrighted through the Office of Innovation and Commercialization at the University of California, San Diego. Cedric Hermans has received consultancy and/or lecture fees from Bayer, Shire/Takeda, Roche, CSL Behring, Novo Nordisk, Octapharma, Sanofi, Pfizer, Sobi, LFB, Octapharma, Uniqure, CSL Behring, and Biomarin. Young‐Shil Park reports research support or participation as a principal investigator from BioMarin Pharmaceutical Inc., CSL Behring, Novo Nordisk, Sanofi, Takeda, Pfizer, and Chugai. Anthony K. C. Chan has received research support from Bayer, Novo Nordisk, Pfizer, Sanofi, and Takeda. He also reports participation in scientific advisory boards and honoraria from Bayer, Novo Nordisk, Octapharma, Pfizer, Sanofi, and Takeda. Alphan Kupesiz reports clinical trials for Bayer, Novo Nordisk, Pfizer, Sanofi, and Roche; and advisory board membership for Novo Nordisk, Roche, Pfizer, Sobi, and Takeda. María Teresa Alvarez‐Román has received consultancy and/or lecture fees from Bayer, Takeda, Roche, CSL Behring, Novo Nordisk, Octapharma, Sanofi, Pfizer, Sobi, LFB, and Biomarin. Lynn Malec has received consultancy fees from Bayer, Sanofi Genzyme, Sobi, Genentech, Biomarin, CSL Behring, Spark Therapeutics, and Novo Nordisk. She has received research funding from Sanofi Genzyme. Elena Santagostino, Linda Bystrická, and Lydia Abad‐Franch are employees of Sobi and may hold shares and/or stock options in the company. Jennifer Dumont, Graham Neill, and Lila‐Sabrina Fetita are employees of Sanofi and may hold shares and/or stock options in the company. Liane Khoo received fees from Biomarin, Bioverativ/Sanofi‐Genzyme, and Roche for participation in industry‐sponsored education events and advisory boards.

Figures

FIGURE 1
FIGURE 1
Major non‐orthopaedic surgeries during XTEND‐1. †Day 0 was the day of surgery. ‡FVIII levels assessed at the central laboratory by aPTT‐based one‐stage clotting assay using Actin FSL. §Postoperative refers to the day following the end of surgery to the date of hospital discharge. During surgical/rehabilitation period, defined as the period beginning with a preoperative loading dose and ending with the latest of hospital discharge; perioperative follow‐up phone call; or end of 2‐week period after the resumption of presurgery treatment regimen. #Calculated as: date of return to PPX − Surgery start date + 1. aPTT, activated partial thromboplastin time; FVIII, factor VIII; NR, not recorded; PPX, prophylaxis; TXA, tranexamic acid.
FIGURE 2
FIGURE 2
Major orthopaedic surgeries during XTEND‐1. †Day 0 was the day of surgery. ‡FVIII levels assessed at the central laboratory by aPTT‐based one‐stage clotting assay using Actin FSL. §Postoperative refers to the day following the end of surgery to the date of hospital discharge. During surgical/rehabilitation period, defined as the period beginning with a preoperative loading dose and ending with the latest of hospital discharge; perioperative follow‐up phone call; or end of 2‐week period after the resumption of presurgery treatment regimen. #Calculated as: date of return to PPX − Surgery start date + 1. aPTT, activated partial thromboplastin time; FVIII, factor VIII; LMWH, low molecular weight heparin; NR, not recorded; PPX, prophylaxis; TXA, tranexamic acid.
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