Long-term Outcomes With Efanesoctocog Alfa Prophylaxis for Previously Treated Children With Severe Hemophilia A, an Interim Analysis of the Phase 3 XTEND-ed Study

Introduction: Efanesoctocog alfa (formerly BIVV001) is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to overcome the von Willebrand factor–imposed half-life ceiling. Once-weekly efanesoctocog alfa 50 IU/kg was well tolerated and provided highly effective bleed protection and factor activity within normal to near-normal levels (>40%) for 3 days, and of ~10% at Day 7, in children with severe hemophilia A in the XTEND-Kids study (NCT04759131). The aim is to evaluate long-term data on safety and efficacy of efanesoctocog alfa in previously treated children with severe hemophilia A in the XTEND-ed study (NCT04644575).

Method: XTEND-ed is a multicenter, open-label study that enrolled participants from previous Phase 3 studies, including children<12 years of age who received weekly efanesoctocog alfa prophylaxis for≤52 weeks in XTEND-Kids, and continue weekly 50 IU/kg prophylaxis in XTEND-ed. The primary endpoint is the occurrence of FVIII inhibitors. Secondary endpoints include annualized bleed rates (ABRs), efficacy for bleed treatment, and safety. Participants provided informed consent and XTEND-ed was approved by applicable ethics committees. First Interim Analysis Data cut: June 8, 2023.

Results: Seventy-one of 74 males (96%) rolled over from XTEND-Kids to XTEND-ed. The mean (standard deviation [SD]) efficacy period was 35.8 (14.1) weeks. No FVIII inhibitors were detected. The mean (SD) ABR was 0.70 (1.27; 6-monthly data: [Fig. 1]), thus maintaining the low mean ABR observed in the parent study (0.88). Most bleeds (86%; 30/35) resolved with a single dose of efanesoctocog alfa 50 IU/kg, with 96% (23/24) of hemostatic responses rated as excellent or good. Overall, 43 (61%) participants experienced≥1 treatment-emergent adverse event (TEAE) and 2 (3%) experienced≥1 serious TEAE ([Fig. 2]).

Fig. 1  Summary of annualized bleed rates by 6-month interval for treated bleeding episodes among children (<12 years old) receiving once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) in XTEND-ed

Fig. 2  Summary of adverse eventsfor children (<12 years old) receiving once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) in XTEND-ed

Conclusion: Long-term results in children with severe hemophilia A in XTEND-ed show that once-weekly efanesoctocog alfa continues to be well tolerated, with no FVIII inhibitors reported, and provides highly effective bleed protection.

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, Bangkok, Thailand. LM participated as a consultant or on advisory boards for Biomarin, CSL Behring, Novo Nordisk, Pfizer, Sanofi, Sobi, Spark Therapeutics, Takeda, as well as speakers’ bureaus for CSL Behring and Sanofi. CK has received personal fees from Bayer Vital GmbH, CSL Behring, Novo Nordisk, Roche/Chugai, Sanofi/Sobi, and Takeda. Dr Königs’s institution has also received grants from Bayer Vital GmbH, Biotest, CSL Behring, Intersero, Novo Nordisk, Pfizer, Roche/Chugai, Sanofi/Sobi, and Takeda. BN has received personal fees from Sobi, and study sponsorship from Bayer, CSL Behring, Sanofi, and Roche. AKCC has been an investigator in clinical trials for Bayer, Novo Nordisk, Pfizer, Sanofi, Takeda and participated in advisory boards for Bayer, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda. MA has received travel support from Sobi. S-CC has received travel support from Sanofi. BZ has received research funding from Pfizer and Takeda and has been a consultant or participated in an advisory board for CSL Behring, Novo Nordisk, Pfizer, Sanofi, and Genveon. MS has been a consultant or participated in an advisory board for Bayer, CSL Behring, Medexus, Novo Nordisk, Pfizer, and Sanofi, as well as speakers’ bureaus for Novo Nordisk. LF, GN, and SG are employees of Sanofi and may hold shares and/or stock options in the company. HP and LA-F are employees of Sobi and may hold shares and/or stock options in the company. KF has received unrestricted grants/research funding from CSL Behring, Sobi for research unrelated to the current study, consultancy fees from Sobi, Sanofi, Takeda, Novo Nordisk, and Roche (all fees to the institution). KF has also participated in other boards, including EAHAD executive committee and the ISTH Standardization Subcommittee on Factor VIII, Factor XI, and Rare Coagulation Disorders.

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Artikel online veröffentlicht:
13. Februar 2025