First Interim Analysis of Clinical Outcomes in Adults and Adolescents With Severe Hemophilia A Receiving Efanesoctocog Alfa Prophylaxis in XTEND-ed, a Phase 3 Long-term Extension Study

S Susen; S P'ng; T Lissitchkov; D Matino; P Chowdary; A Weyand; R Klamroth; Y-S Park; M T Alvarez-Román; L Feng; H Palmborg; J Dumont; E Santagostino; L-S Fetita; K Nogami

doi:10.1055/s-0044-1801608

Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 2025; 45(S 01): S42-S43
DOI: 10.1055/s-0044-1801608

Abstracts

Topics

T-07 Hereditary bleeding disorders

First Interim Analysis of Clinical Outcomes in Adults and Adolescents With Severe Hemophilia A Receiving Efanesoctocog Alfa Prophylaxis in XTEND-ed, a Phase 3 Long-term Extension Study

S Susen

¹Centre Hospitalier Universitaire de Lille, Université de Lille, Lille, France

,

S P'ng

²Fiona Stanley Hospital, The Haemophilia and Haemostasis Centre, Murdoch, Australia

,

T Lissitchkov

³Specialized Hospital for Active Treatment of Hematological Diseases, Department of Chemotherapy, Hemotherapy and Hereditary Blood Diseases at Clinical Hematology Clinic, Sofia, Bulgaria

,

D Matino

⁴McMaster University, Division of Hematology & Thromboembolism, Department of Medicine, Ontario, Canada

,

P Chowdary

⁵Royal Free Hospital, Katharine Dormandy Haemophilia and Thrombosis Centre, London, UK

,

A Weyand

⁶University of Michigan Medical School, Division of Hematology/Oncology, Department of Pediatrics, Ann Arbor, USA

,

R Klamroth

⁷Vivantes Klinikum, Friedrichshain, Berlin, Germany

,

Y-S Park

⁸Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Department of Pediatrics, Seoul, South Korea

,

M T Alvarez-Román

⁹University Hospital La Paz, Autonoma University of Madrid, Department of Hematology, Madrid, Spain

,

L Feng

¹⁰Sanofi, Shanghai, China

,

H Palmborg

¹¹Sobi, Stockholm, Sweden

,

J Dumont

¹²Sanofi, Cambridge, USA

,

E Santagostino

¹³Sobi, Basel, Switzerland

,

L-S Fetita

¹⁴Sanofi, Paris, France

,

K Nogami

¹⁵Nara Medical University, Nara, Japan

› Institutsangaben

Abstract

Volltext

Introduction: Efanesoctocog alfa (formerly BIVV001) is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to decouple FVIII from endogenous von Willebrand factor. In the Phase 3 XTEND-1 study (NCT04161495), once-weekly efanesoctocog alfa demonstrated superior bleed protection over prior prophylaxis, was well tolerated, and provided FVIII activity within the normal to near-normal (>40%) range for most of the week. The aim is to evaluate long-term safety and efficacy of efanesoctocog alfa in adults/adolescents with severe hemophilia A from XTEND-ed (NCT04644575).

Method: Previously treated patients (≥12 years old) who completed XTEND-1 (Arm A/B) could continue once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis in the multicenter, open-label, long-term XTEND-ed study. The primary endpoint is incidence of FVIII inhibitor development. Secondary endpoints include annualized bleed rates (ABRs), efficacy for bleed treatment, and safety. XTEND-ed was approved by local ethics committees; participants provided informed consent. First interim analysis data cut: June 8, 2023.

Results: A total of 146 patients (including 1 female) rolled over from XTEND-1 to XTEND-ed (12–17 years, n=21; 18–64 years, n=120;≥65 years, n=5). Mean (range) treatment duration in XTEND-ed was 82.5 (14.1–103.6) weeks. FVIII inhibitors were not detected. Mean (standard deviation) ABR during XTEND-ed for patients from XTEND-1 Arms A and B was 0.72 (1.26) and 0.42 (0.89), respectively (6-monthly data: [Fig. 1]), thus maintaining the low mean ABRs observed in the parent study (Arm A: 0.71; Arm B: 0.69). Most (94%; 142/151) bleeding episodes resolved with 1 injection of efanesoctocog alfa; response was rated by participants as excellent/good for 88% (108/123) of bleeds. Overall, 108 (74%) participants experienced≥1 treatment-emergent adverse event (TEAE) and 17 (12%) experienced≥1 serious TEAE ([Fig. 2]).

Fig. 1 Summary of annualized bleed rates by 6-month interval for treated bleeding episodesin adults and adolescents receiving once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) in XTEND-ed stratified by treatment arm of XTEND-1

Fig. 2 Summary of adverse eventsamong adults and adolescents receiving once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) in XTEND-ed

Conclusion: Long-term results in adults/adolescents in XTEND-ed show that once-weekly efanesoctocog alfa continues to be well tolerated and highly effective. No inhibitors were detected and ABRs remained low.

Funded by Sanofi and Sobi.

Abbildungen

Fig. 1 Summary of annualized bleed rates by 6-month interval for treated bleeding episodesin adults and adolescents receiving once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) in XTEND-ed stratified by treatment arm of XTEND-1

Fig. 2 Summary of adverse eventsamong adults and adolescents receiving once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) in XTEND-ed