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.

 

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Conflict of Interest:

Data first presented at International Society on Thrombosis and Haemostasis (ISTH) 2024, June 22–26, 2024. AKCC has participated in clinical trials for Bayer, Novo Nordisk, Pfizer, Sanofi and was an advisory board member for Bayer, Novo Nordisk, Octapharma, Sanofi, and Takeda. SS has participated in scientific advisory boards for BioMarin, CSL Behring, LFB, Roche, Novo Nordisk, Sanofi, Sobi, and Takeda. SS also received support from BioMarin, Bioverativ, CSL Behring, CorWave, Roche-Chugai, Sanofi, Shire/Takeda, Siemens Healthineers, Sobi, and Stago LFB. LK has received fees from Biomarin, Bioverativ/Sanofi-Genzyme, and Roche for participation in industry-sponsored education events and advisory boards. AVD has received research support from Bioverativ, Sanofi, and Pfizer. AVD has participated on scientific advisory boards for BioMarin, Bioverativ/Sanofi, CSL Behring, Genentech, Pfizer, Regeneron, Novo Nordisk, Takeda. She is also a co-founder and member of the board of directors of Hematherix Inc and holds a patent for a super FVa, as well as being an inventor and physician lead for the Joint Activity and Damage Examination (JADE) ultrasound measurement tool. JO has received research funding from Bayer, Biotest, CSL Behring, Octapharma, Pfizer, Swedish Orphan Biovitrum, and Takeda; consultancy, speakers bureau, honoraria, scientific advisory board and travel expenses from Bayer, Biogen Idec, BioMarin, Biotest, Chugai, CSL Behring, Freeline, Grifols, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Spark Therapeutics, Swedish Orphan Biovitrum, and Takeda. MCS has received research grants from Sanofi. FP is a member of advisory committees of Biomarin, Sanofi, Sobi, CSL Behring, Roche, and received speaker fee for participation at educational meetings from Takeda and Spark. CT has received honoraria for advisory board from Sanofi and serves on a study steering committee for Bayer. PC has served on advisory boards for Apcintex, Bayer, Boehringer Ingelheim, Baxalta/Shire, Biogen Idec, CSL Behring, Chugai, Freeline, Novo Nordisk, Pfizer, Roche, Sanofi, and Sobi, and has received research funding from Bayer, CSL Behring, Novo Nordisk, Pfizer, and Sobi. LM, and JD are employees of Sanofi and may hold shares and/or stock options in the company. HP and ES are employees of Sobi and may hold shares and/or stock options in the company. CH 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.

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Artikel online veröffentlicht:
13. Februar 2025