Entering a New Era in
Protection in Haemophilia A
Chairperson: Jan Astermark1,2 Speakers: Maria Elisa Mancuso,3,4 Christoph Königs,5 Robert Klamroth6,7
Department of Translational Medicine, Lund University, Sweden
Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden
Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital, Milan, Italy
Humanitas University, Milan, Italy
Department of Paediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Goethe University, University Hospital, Frankfurt, Germany
Department of Internal Medicine, Vascular Medicine and Haematology, Vivantes Klinikum Friedrichshain, Berlin, Germany
Haemophilia Treatment Centre, Vivantes Klinikum Friedrichshain, Berlin, Germany
Disclosure: Astermark was principal investigator (PI) or has received research support or grant funding from CSL Behring, SobiTM, and Takeda; been a consultant for Bayer, BioMarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Sanofi, SobiTM, and Takeda; received speaker’s fees from Bayer, BioMarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, and SobiTM; and has participated on scientific Advisory Boards for Bayer, BioMarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, SobiTM, and Takeda. Mancuso was PI or has received research support or grant funding from Bayer, CSL Behring, Novo Nordisk, and Takeda; been a consultant for Bayer, BioMarin, CSL Behring, Kedrion, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, and SobiTM; received speaker’s fees from Bayer, CSL Behring, Kedrion, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, and SobiTM; and has participated on scientific Advisory Boards for Bayer, BioMarin, CSL Behring, Kedrion, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, SobiTM, and Takeda. Königs was PI or has received research support or grant funding from Bayer, Biotest, CSL Behring, Intersero, Novo Nordisk, Pfizer, Roche/Chugai, Sanofi, SobiTM, and Takeda; received speaker’s fees from BFSH, Bayer, CSL Behring, Novo Nordisk, Roche/Chugai, SobiTM, and Takeda; and has participated on scientific Advisory Boards for CSL Behring, Novo Nordisk, Pfizer, Roche/Chugai, and SobiTM. Klamroth was PI or has received research support or grant funding from Novo Nordisk, Octapharma, and SobiTM; been a consultant for Bayer, Biotest, BioMarin, CSL Behring, Grifols, Kedrion, LFB, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, SobiTM, and Takeda; received speaker’s fees from Bayer, Biotest, BioMarin, CSL Behring, Grifols, Kedrion, Leo, LFB, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, SobiTM, Takeda, and Viatris; and has participated on scientific Advisory Boards for Bayer, Biotest, BioMarin, CSL Behring, Grifols, Kedrion, Leo, LFB, Novo Nordisk, Octapharma, Pfizer, Roche/ Chugai, Sanofi, SobiTM, and Takeda.
Acknowledgements: Medical writing assistance was provided by Leonie Glasson, AMICULUM, Bollington, UK.
Disclaimer: The views and opinions expressed are those of the authors and not necessarily of SobiTM.
Keywords: Factor VIII (FVIII), haemophilia A (HA), haemostasis, health equity, normalisation.
Original Citation: EMJ Hematol. 2025;13[Suppl x]:xx-xx. https://doi.org/10.33590/emjhematol/THKR9677
Support: The symposium and the publication of this article were funded by SobiTM. Approval number: NP-47654 - March 2026
Summary
Haemophilia A (HA), defined by factor VIII (FVIII) levels ≤40 IU/dL, is a chronic condition with consequences beyond bleeding complications. Jan Astermark (Professor of Clinical Coagulation Medicine, Senior Consultant, and Head of Department of Translational Medicine, Lund University; and Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden) outlined the burden of HA on the quality of life (QoL) of patients, including bleeding, joint damage, pain, psychosocial wellbeing, and physical activity. He shared real-world evidence showing that current prophylactic regimens with FVIII or non-factor therapy (NFT) are not sufficient to eliminate all types of bleeds and that many challenges remain. Astermark presented several analyses highlighting that FVIII levels in the non-haemophilia range may be necessary to prevent residual bleeding. These analyses have informed recent treatment goals that transcend historical targets of converting severe HA (SHA) into moderate or mild forms and aim towards normalised haemostasis to eliminate bleeds. Maria Elisa Mancuso (Senior Consultant in Haematology, Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital and Humanitas University, Milan, Italy) presented a patient case to illustrate the challenges that people with HA (PwHA) face over their lives and the evolution of treatment strategies to address unmet needs. Christoph Königs (Head of Clinical and Molecular Haemostasis at the Department of Paediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Goethe University, University Hospital, Frankfurt, Germany) emphasised the unique challenges faced by children with HA and their caregivers, including restrictions in daily activities, regular evaluations for subclinical and evident bleeds, long-term joint protection, delayed inhibitor development, self-injection skills, and suboptimal adherence. He discussed how standard and extended half-life (SHL, EHL) therapies have improved care in children with HA but highlighted how prophylaxis with existing therapies is not sufficient to eliminate evident and subclinical bleeds. He concluded by sharing data on novel therapies that offer the potential to maintain FVIII levels in the non-haemophilia range (≥40 IU/dL) to help address these unmet needs. Robert Klamroth (Head of the Department of Internal Medicine, Vascular Medicine and Haematology, and Director of Haemophilia Treatment Centre, at Vivantes Klinikum Friedrichshain, Berlin, Germany) focused on the evolving challenges of HA in adulthood, including surgery and the need for anticoagulant or antiplatelet therapy for the management of comorbidities. Recent clinical data were shown to demonstrate how high sustained FVIII levels could minimise bleeding risk and improve joint health, surgical management, and overall QoL in adults with HA. In the panel discussion, two patient cases were reviewed to consider unmet needs in people with mild HA and in elderly people with HA, and the panel summarised how sustaining FVIII levels in the non-haemophilia range could help address these needs. The panel concluded by reviewing the evolution of treatment strategies and the importance of targeting normalised haemostasis in a new era of protection in HA.
Summary
Hematology
WELCOME & INTRODUCTION
Jan Astermark
In a real-world cross-sectional survey of 244 people with severe or moderate HA treated with prophylaxis in the USA:
Professor of Clinical Coagulation Medicine, Senior Consultant, and Head of Department of Translational Medicine, Lund University; and Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden
Bleeding and joint problems, in turn, have a significant burden on patients’ QoL, with:1
Recent analyses indicate that sustained time in the non-haemophilia range (FVIII levels ≥40 IU/dL) may be a necessary first step to elevating the standard of care in PwHA (Figure 1).2-6
Targeting FVIII levels ≥40 IU/dL could improve clinical outcomes and the QoL of PwHA by reducing the risk of clinical and subclinical bleeds, improving long-term joint health, and reducing synovitis, joint damage, and pain.2-5
This symposium discussed a new era of protection in haemophilia A and explored how novel therapies may help achieve normalised haemostasis which could improve the physical and mental wellbeing of PwHA.
FVIII: factor VIII; PwHA: people with haemophilia A; QoL: quality of life.
Sustaining normalised haemostasis could improve QoL by reducing the ongoing emotional burden caused by bleeds, pain and limitations in everyday life
Figure 1: Normalisation of haemostasis as the beginning of the journey to elevate standards of care2–6
Optimising protection with sustained high FVIII levels
With sustained time above 40 IU/dL, PwHA can maintain improved protection
Figure 1: Normalisation of haemostasis as the beginning of the journey to elevate standards of care2–6
Sustaining normalised haemostasis could improve QoL by reducing the ongoing emotional burden caused by bleeds, pain and limitations in everyday life
FVIII: factor VIII; PwHA: people with haemophilia A; QoL: quality of life.
Optimising protection with sustained high FVIII levels
With sustained time above 40 IU/dL, PwHA can maintain improved protection
With improved protection, the risk of both clinical and subclinical bleeds is reduced
Preventing both clinical and subclinical bleeding
Figure 1: Normalisation of haemostasis as the beginning of the journey to elevate standards of care2–6
Sustaining normalised haemostasis could improve QoL by reducing the ongoing emotional burden caused by bleeds, pain and limitations in everyday life
FVIII: factor VIII; PwHA: people with haemophilia A; QoL: quality of life.
Optimising protection with sustained high FVIII levels
With sustained time above 40 IU/dL, PwHA can maintain improved protection
With improved protection, the risk of both clinical and subclinical bleeds is reduced
Preventing both clinical and subclinical bleeding
By preventing both clinical and subclinical bleeds, long-term joint health outcomes can be improved
Addressing the burden of joint damage and pain
Figure 1: Normalisation of haemostasis as the beginning of the journey to elevate standards of care2–6
Sustaining normalised haemostasis could improve QoL by reducing the ongoing emotional burden caused by bleeds, pain and limitations in everyday life
FVIII: factor VIII; PwHA: people with haemophilia A; QoL: quality of life.
Optimising protection with sustained high FVIII levels
With sustained time above 40 IU/dL, PwHA can maintain improved protection
With improved protection, the risk of both clinical and subclinical bleeds is reduced
Preventing both clinical and subclinical bleeding
By preventing both clinical and subclinical bleeds, long-term joint health outcomes can be improved
Addressing the burden of joint damage and pain
With improved long-term joint health, PwHA can avoid pain, restricted mobility and impaired QoL caused by arthropathy
Resulting in better QoL
This symposium took place on 5th February as part of the Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) 2025, held in Milan, Italy, between 4th–7th February 2025
Evolving Goals in Haemophilia A: From Concept to Reality
Mancuso illustrated the challenges associated with HA and the evolution of treatment strategies via the example case of a male patient who was diagnosed with SHA at 14 months old following a gluteus haematoma.
Senior Consultant in Haematology, Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital and Humanitas University, Milan, Italy
Maria Elisa Mancuso
Childhood
Adolescence
Adulthood
Ageing
CHILDHOOD
To manage the gluteus haematoma, the patient was treated with SHL-FVIII and started on regular prophylaxis to minimise the risk of future bleeds.
SHL-FVIII: Standard half-life factor VIII
ADOLESCENCE
When he was 11 years old, the first EHL-FVIII
became available, but his parents were reluctant to switch his treatment in fear of inhibitor development.
EHL-FVIII: Extended half-life factor VIII
He continued on SHL-FVIII until, after recurrent target joint bleeds, he decided to switch to EHL recombinant FVIII (rFVIII) at 15 years old.
ADULTHOOD
The patient continued his treatment of EHL-rFVIII but variable venous access and a reluctance to inject at inconvenient times resulted in suboptimal adherence.
NFT: Non-factor therapy
AGEING
Despite his treatment programme, his knee pain continued, and the patient was indicated for knee replacement surgery when he was 42 years old.
Summary
Mancuso concluded her presentation by summarising the evolution of treatment strategies.
Head of Clinical and Molecular Haemostasis at the Department of Paediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Goethe University, University Hospital, Frankfurt, Germany
Christoph Königs
Realising New Possibilities for Children with Haemophilia A
Königs emphasised the unique challenges faced by children with HA and their caregivers, including the risk of inhibitor development, lack of self-injection skills, suboptimal adherence, the need for regular evaluations of subclinical and joint bleeds, and limitations in physical activities (Figure 2).
Children with HA can be affected by significant joint and muscle bleeding.
Current treatment approaches for children
Advances to sustain FVIII levels within the non-haemophilia range could help to prevent evident and subclinical bleeding in PwHA.
In a UK cohort of 237 PwHA (including 80 children <18 years) selected for high compliance with EHL or SHL prophylaxis, 32.5% were affected by joint bleeds.13
Königs emphasised that in a real-world, retrospective, multi-institutional cohort of 314 children and young adults with HA receiving NFT, 15 patients (including four with inhibitors) experienced 19 muscle bleeds that required intensive and prolonged factor treatment.14
Impaired joint health in the absence of reported bleeding was also documented in a cross-sectional study of 106 children (636 joints) with SHA on prophylaxis, where 50% scored >0 in Hemophilia Early Arthopathy Detection with Ultrasound (HEAD-US) and 13% of joints with no bleeding history were scored ≥1 in HEAD-US.9
Children with HA can be affected by significant joint and muscle bleeding.
Current treatment approaches for children
Among the current treatment approaches for children, emicizumab is an NFT indicated in the European Union as routine prophylaxis in PwHA of all ages with FVIII inhibitors and in those without FVIII inhibitors if they have SHA or moderate HA with a severe bleeding phenotype.15
Advances to sustain FVIII levels within the non-haemophilia range could help to prevent evident and subclinical bleeding in PwHA.
Head of the Department of Internal Medicine, Vascular Medicine and Haematology, Vivantes Klinikum Friedrichshain, Berlin, Germany; Haemophilia Treatment Centre, Vivantes Klinikum Friedrichshain, Berlin, Germany
Robert Klamroth
Adults living with SHA face multiple challenges, including healthcare dependency, evident and subclinical bleeds, physical activity limitations, surgeries, and comorbidities requiring concomitant medications, including anticoagulants and antiplatelets.10,14,23-33
Transforming Clinical Perspectives in Adults with Haemophilia A
Sustaining FVIII levels in the non-haemophilia range
Targeting FVIII levels in the non-haemophilia range is supported by data from a Phase III gene therapy trial, which found that 100% of patients (n=11) with FVIII levels ≥40 IU/ dL had zero treated bleeds after Year 2 (Figure 3).37
Efanesoctocog was overall well tolerated.
No FVIII inhibitors were detected.
Two patients experienced thromboembolic events: one was a deep vein thrombosis following corrective surgery for a femur fracture (in the setting of treatment with another FVIII product), and the other was a cerebral infarction in a patient with pre-existing atrial fibrillation and other risk factors; neither event was related to efanesoctocog alfa treatment.
Two related treatment-emergent adverse events were reported (facial paralysis and locally measured coagulation FVIII level decrease), and both events resolved.39-41
In PwHA, surgery requires careful management of bleeding risk by maintaining high perioperative FVIII levels.
Transitioning From Clinical Trials to Real-World Practice
Speaker presentations were followed by a faculty discussion of two patient cases to demonstrate the challenges of PwHA.
Faculty conclusion
BACK TO CHILDHOOD
In children, venous access can be a challenge; for this child, it led to skipped infusions and suboptimal protection.
He experienced recurrent joint bleeds and so began prolonged treatment with a central venous line to help optimise prophylaxis.
At 8 years old, he experienced a central venous line infection that necessitated a temporary stop in SHL-FVIII, but his regular treatment was resumed once the infection subsided.
Efficacy and safety of efanesoctocog alfa from the XTEND-ed trial
llustration of potential challenges over the lifespan.
Treatments for HA historically focused on converting severe disease (FVIII <1 IU/dL) into moderate forms (FVIII ~1-5 IU/dL) to minimise life-threatening bleeds.7
Improvements in care were observed with EHL therapies and NFTs; however, these are not sufficient to fully protect patients from bleeds, including subclinical and joint bleeds.6
With the development of novel treatment options, including ultra-long FVIII replacement therapy, it is feasible to now target more ambitious goals of normalised haemostasis.8
PWHA and their caregivers aspire to future treatments that are less invasive, longer-acting, and more convenient to reduce the physical and emotional burden thereby improving overall QoL.8
In the Phase Illb HAVEN 7 trial, emicizumab prophylaxis demonstrated efficacy and a favourable safety profile in 55 infants aged ≤1 year with SHA without inhibitors.16
After a median efficacy period of 101.9 weeks, the model-based mean (95% CI) annualised bleeding rate (ABR) was 0.40 (0.30-0.63) for treated bleeds, and
In a German survey (N=685), including adults with HA (N=513), pain prevalence increased with age, and over two-thirds of patients aged >40 years reported frequent joint pain.35
In a Phase III, open-label, multicentre study of PwSHA, patients reporting no pain were significantly more likely to have zero bleeds (57%) than patients reporting pain (43%; p<0.05).36
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Figure 3: Maintaining FVIII levels in the non-haemophilia range could help achieve the goal of zero bleeds37