-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3993 Treatment of Bleeding Episodes with Efanesoctocog Alfa in Children with Severe Hemophilia A in the XTEND-Kids Phase 3 StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Bleeding and Clotting, Research, clinical trials, hemophilia, Clinical Research, Diseases
Monday, December 11, 2023, 6:00 PM-8:00 PM

Lynn Malec, MD1,2,3, Amy Dunn, MD4,5, Manuel Carcao, MD, FRCP(C)6*, Bulent Zulfikar7*, Ruben Berrueco8*, Simon Brown9, Umer Khan10*, Sriya Gunawardena11*, Graham Neill12*, Lydia Abad-Franch13*, Linda Bystrická14*, Elena Santagostino13 and Sophie Susen15*

1Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI
2Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
3Versiti Blood Research Institute, Milwaukee, WI
4The Division of Hematology/Oncology/BMT, Nationwide Childrens Hospital, Columbus, OH
5The Division of Hematology/Oncology/BMT, The Ohio State University College of Medicine, Columbus
6Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
7Inherited Bleeding Disorders Center, Istanbul University Oncology Institute, Istanbul, Turkey
8Pediatric Hematology Department, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
9Queensland Children’s Hospital, South Brisbane, Australia
10Sanofi, Cambridge, MA
11Sanofi, Bridgewater
12Sanofi, Reading, United Kingdom
13Sobi, Basel, Switzerland
14Sobi, Stockholm, Sweden
15Centre Hospitalier Universitaire de Lille, Lille, France


Efanesoctocog alfa (formerly BIVV001) is a new class of high sustained factor VIII (FVIII) replacement therapy, composed of a single recombinant FVIII protein fused to dimeric Fc protein, 2 XTEN polypeptides, and the D’D3 domain of von Willebrand factor (VWF), designed to overcome the endogenous VWF-imposed half-life ceiling. The XTEND-Kids (NCT04759131) study demonstrated once-weekly efanesoctocog alfa was well tolerated and provided effective treatment of and protection from bleeds in previously treated patients <12 years old with severe hemophilia A. Here, we provide a detailed report on efanesoctocog alfa as a treatment for bleeds during XTEND-Kids.


Previously treated patients <12 years old (≥150 exposure days [EDs] for patients 6 to <12 years of age and ≥50 EDs for patients <6 years old) with severe hemophilia A (<1 IU/dL [<1%] endogenous FVIII activity or a documented genotype associated with severe hemophilia) received efanesoctocog alfa 50 IU/kg once weekly for 52 weeks. In line with the study protocol, bleeds were treated with a single dose of efanesoctocog alfa (50 IU/kg). Additional doses (30 or 50 IU/kg, every 2–3 days) could be considered if needed. For minor/moderate bleeds occurring within 2–3 days of a recent prophylactic dose, a 30 IU/kg dose could also be used. The number and location of bleeds, as well as dose and number of efanesoctocog alfa injections required to resolve them were recorded. Patient assessment of the response to the first injection for treating a bleed was evaluated using the 4-point International Society on Thrombosis and Haemostasis (ISTH) scale (excellent, good, moderate, and none).


Of 74 patients in XTEND-Kids, 73 were included in these post hoc analyses, including 38 subjects <6 years of age. One subject in the 6 to <12 group was excluded from these analyses as he did not receive weekly prophylaxis treatment as specified in the protocol, instead receiving intense consolidation treatment (2–3 injections per week for ~4 months) following 2 traumatic self-reported hip bleeds (however, no signs of bleeding or joint damage were observed by magnetic resonance imaging during the consolidation treatment period).

The mean (SD) total number of EDs was 52.3 (6.83) for the overall population. The mean (95% confidence interval [CI]) estimated annualized bleed rate (ABR) was 0.61 (0.42–0.90). The mean (95% CI) annualized spontaneous, traumatic, and joint bleed rates were 0.16 (0.08–0.31), 0.40 (0.24–0.65), and 0.30 (0.16–0.57), respectively. Eighty-six percent of participants (n=63) had ≤1 bleed, including 64% (n=47) with no overall bleeds; 88% (n=64) had no spontaneous bleeds and 84% (n=61) had no joint bleeds. There were 43 bleeds treated with efanesoctocog alfa, of which 11 were reported as spontaneous (26%), 28 as traumatic (65%), and 4 (9%) were of unknown etiology (Table). The most common locations for bleeds were the joints (n=21, 49%) and skin/mucosa (n=15, 35%). The rate of bleeding events per week throughout the study remained consistently low (Figure). The mean (SD) duration between a treated bleed and nearest injection taken prior to that bleed was 4.7 (1.95) days, with a mean of 4.5 (1.56) days for a spontaneous bleed and 4.8 (2.12) for traumatic bleeds. A single injection was sufficient to resolve 95% of bleeds, and no bleed required more than 2 injections for resolution. The median (interquartile range) total dose required to resolve a bleed was 52.6 (50.0–55.8) IU/kg. Among first injections for bleeding episodes with an evaluation of response by participants (n=37), the vast majority (n=36, 97%) were rated as excellent or good.


A single dose of efanesoctocog alfa 50 IU/kg resolved 95% of bleeds in children <12 years of age, regardless of type or location. The hemostatic efficacy of efanesoctocog alfa was rated as excellent or good for nearly all evaluated first injections (97%). Once-weekly efanesoctocog alfa provided efficient prophylaxis with no bleeds in 64% of participants, and consistently low ABRs among all types and locations of bleeds. Efanesoctocog alfa provided effective treatment and prevention of bleeds in previously treated children <12 years of age with severe hemophilia A.

Disclosures: Malec: Novo Nordisk: Honoraria; Genentech: Honoraria; Spark Therapeutics: Honoraria; CSL: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Sobi: Honoraria. Dunn: Nationwide Children’s Hospital: Current Employment; World Federation of Hemophilia-USA: Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; Biomarin: Consultancy, Honoraria, Research Funding; Sanofi/Sobi: Consultancy, Research Funding; Hema Biologics: Consultancy; Takeda: Research Funding; Pfizer: Research Funding; CSL Behring: Consultancy; Genentech: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; American Thrombosis and Hemostasis Network: Honoraria, Research Funding; Regeneron: Consultancy, Research Funding; Pfizer: Research Funding; Spark: Research Funding. Carcao: Roche: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Novartis: Research Funding; Bioverativ/Sanofi: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Shire/Takeda: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; CSL Behring: Honoraria; LFB: Honoraria. Zulfikar: SOBI: Consultancy, Honoraria, Speakers Bureau; SANOFI: Consultancy, Honoraria; PFIZER: Consultancy, Research Funding; NOVO NORDISK: Consultancy, Honoraria, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Speakers Bureau; CSL BEHRING: Consultancy, Honoraria, Speakers Bureau; GENVEON: Consultancy, Honoraria, Speakers Bureau. Berrueco: Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SOBI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Khan: Sanofi: Current Employment. Gunawardena: Sanofi: Current Employment, Current equity holder in publicly-traded company. Neill: Sanofi: Current Employment, Current equity holder in publicly-traded company. Abad-Franch: Sobi: Current Employment. Bystrická: Swedish Orphan Biovitrum AB: Current Employment, Current equity holder in publicly-traded company. Santagostino: Swedish Orphan Biovitrum: Current Employment. Susen: BIOMARIN: Consultancy, Membership on an entity's Board of Directors or advisory committees; SANOFI: Consultancy; ROCHE/CHUGAI: Consultancy, Research Funding; Novo Nordisk: Consultancy; CSL-Behring: Consultancy, Research Funding; SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH