Publication Number: 305

 

Abstract Title : Emicizumab prophylaxis in pups and mtps with severe haemophilia: The pednet real world experience in 80 infants

 

Category: 300s - Hemostasis, Thrombosis and Vascular Wall Biology

 

Review Category: 322. Hemophilia A and B: Clinical and Epidemiological

Authors

 

Marloes de Kovel¹, Gili Kenet², Jayashree Motwani³, Nadine G. Andersson^{4, 5, 6}, Jan Blanty⁷, Giancarlo Castaman⁸, Manuel Carcao⁹, Carmen Escuriola-Ettingshausen¹⁰, Chris Königs¹¹, Christoph Male¹², Beatrice Nolan¹³, Martin Olivieri¹⁴, Caroline Oudot¹⁵, Eleni Pergantou¹⁶, Susanna Ranta¹⁷, Ester Zapotocka¹⁸, Kathelijn Fischer^{1, 19}

 

¹ PedNet Haemophilia Research Foundation, Baarn, Netherlands, ² National Hemophilia Center, Sheba Medical Center, Tel Hashomer and Amalia Biron Research Institute of Thrombosis and Hemostasis, Tel Aviv University, Tel Hashomer, Israel, ³ Birmingham Children's Hospital NHS Foundation Trust, Department of Oncology & Haematology, Birmingham, United Kingdom, ⁴ Skåne University Hospital, Center for Thrombosis and Haemostasis, Malmö, Sweden, ⁵ Skåne University Hospital, Department of Paediatric Haematology and Oncology, Lund, Sweden, ⁶ Lund University, Department of Clinical Sciences and Paediatrics, Lund, Sweden, ⁷ Department of Paediatric Haematology and Biochemistry, University Hospital Brno and Masaryk University, Brno, Czech Republic, ⁸ Careggi University Hospital, Department of Heart, Lung and Vessels, Florence, Italy, ⁹ The Hospital for Sick Children and University of Toronto, Division of Haematology/Oncology, Department of Paediatrics,, Toronto, Canada, ¹⁰ HZRM - Hämophilie-Zentrum Rhein Main GmbH, Frankfurt, Germany, ¹¹ Goethe University Frankfurt, University Hospital, Department of Paediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Frankfurt, Germany, ¹² Medical University of Vienna, Department of Paediatrics, Vienna, Austria, ¹³ Children’s Health Ireland at Crumlin, Department of Paediatric Haematology, Dublin, Ireland, ¹⁴ Paediatric Haemophilia Center, Dr. von Hauner Children's Hospital, LMU Munich, Paediatric Thrombosis and Haemostasis Uni, Munich, Germany, ¹⁵ Centre Régional d'Hémophilie CHU de Toulouse - Hôpital Purpan, Toulouse, France, ¹⁶ Aghia Sophia Children's Hospital, Haemophilia Centre for children/Haemostasis and Thrombosis Unit, Athens, Greece, ¹⁷ Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden, ¹⁸ University Hospital Motol, Department of Paediatric Haematology/Oncology, Prague, Czech Republic, ¹⁹ Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrech, Utrecht, Netherlands

 

Abstract Body

 

Emicizumab (Hemlibra®, Roche) is a humanized bispecific antibody used for subcutaneous prophylaxis in children of any age and adults with haemophilia A (HA). While the HAVEN-7 trial provided primary data on 55 infants with severe HA without FVIII inhibitors, real-world data regarding this age group remains limited. To address this, we analysed prospectively collected data on inhibitor development and bleeding in emicizumab-treated previously untreated patients (PUPs) and minimally treated patients (MTPs; i.e. <6 exposure days (EDs) to FVIII) at PedNet Centres.

 

Data were extracted from the PedNet Registry (a prospective, observational multicentre study collecting data from 34 haemophilia treatment centres in 19 countries), as of January 1, 2025, focusing on children with severe HA without inhibitors who started emicizumab as either PUPs or MTPs, and had received emicizumab prophylaxis for ≥12 weeks. Children included in the HAVEN-7 trial were excluded. Ethical approval was obtained from the parents/guardians of all participants. Key endpoints were inhibitor development, and bleeding rates, including the proportion of children with zero treated bleeds.

 

We analysed 80 infants (39/80 were PUP) with a median follow-up of 84.5 weeks and a median age at emicizumab initiation of 8.6 months (P25-P75 6.7-11.3; range 0.2-26.4). During follow-up, 46/80 infants received FVIII for bleeding episodes (median 3 (P25-P75 1-6; range 1-108 lifetime EDs)) and/or concomitant prophylaxis (n=10). The model-based annualized bleeding rate was 0.6 (95%CI 0.4 – 1.1) with 56% experiencing zero treated bleeds, and no serious adverse events or thromboses were reported. Five infants (2 MTPs) developed FVIII inhibitors (3 high responders (>5.0 BU/mL)) after 4-18 exposure days to FVIII. These data support the safety and efficacy of early emicizumab prophylaxis. However, long-term effects on FVIII inhibitor development require further investigation.

 

 

 

Keywords: Research, Clinical Research, Pediatric, Neonatal, Hemophilia, Diseases, Epidemiology, Real-World Evidence, Study Population, Human, Registries, Bleeding and Clotting

 

Disclosure : Marloes de Kovel: None declared, Gili Kenet: Novo Nordisk, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Alnylam, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Roche, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, BioMarin Pharmaceutical, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL Bering, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Shire, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Pfizer, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, BPL, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Opko Biologics, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, uniQure, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Jayashree Motwani: None declared, Nadine G. Andersson: NovoNordisk, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, CSL Behring, Octapharma, Sobi, Sanofi, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Jan Blanty: Ministry of Health, Czech Republic (FNBr, 65269705), Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Roche, Sobi, NovoNordisk, Pfizer, Takeda, Octapharma, CSL Behring, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Giancarlo Castaman: Bayer, Bioviiix, CSL Behring, LFB, Novo Nordisk, Pfizer, Roche, Sobi/Sanofi, Takeda, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL Behring, Pfizer, and SOBI, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Manuel Carcao: Bayer, Bioverativ/Sanofi, Novartis, Novo Nordisk, Pfizer, Roche and Shire/Takeda, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Bayer, Bioverativ/Sanofi, CSL Behring, LFB, Novo Nordisk, Pfizer, Roche, and Shire/Takeda, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Carmen Escuriola-Ettingshausen: Takeda, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Biotest, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sobi, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, BioMarin, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisk, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, OctaPharma, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, LFB, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Roche/Chugai, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chris Königs: Bayer, Biotest, CSL Behring, Intersero, Novo Nordisk, Pfizer, Roche/Chugai, Takeda, Sobi/Sanofi, EU H2020 ITN, State of Hesse, FUSE e.V, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Bayer, CSL Behring, Florio, MSD, Novo Nordisk, Roche/Chugai, Sobi/Sanofi and Takeda, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Christoph Male: Bayer, Biomarin, Biotest, CSL Behring, LFB, Novo Nordisk, Pfizer, Roche, SOBI, Takeda, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Biotest, CSL Behring, Novo Nordisk, SOBI, Takeda, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Beatrice Nolan: SOBI, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Martin Olivieri: Bayer, Biomarin, NovoNordisk, Takeda, CLS Behring, Pfizer, Roche and Swedish Orphan Biovitrum, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Biomarin, Takeda, CSL Behring, Octapharma, Pfizer, Shire, Roche, Stago and Swedish Orphan Biovitrum, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Caroline Oudot: SOBI, OCTAPHARMA and LFB, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Eleni Pergantou: None declared, Susanna Ranta: Childhood Cancer Foundation, Ellen Bachrach Memorial Fund and Stockholm County Council, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Roche and NovoNordisk, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No, Ester Zapotocka: NovoNordisk, Roche, Sobi and Takeda, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Kathelijn Fischer: Bayer, NovoNordisk, Pfizer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Biogen, CSL Behring, NovoNordisk, and SOBI, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: No