At the 2026 European Hematology Association (EHA) Annual Meeting, Professor Pratima Chowdary from the Katherine Dormandy Haemophilia and Thrombosis Centre at Royal Free Hospital, University College London (UCL), delivered an in-depth presentation titled "The future of hemophilia care: Entering an era of personalized medicine." Professor Chowdary reviewed the evolution of hemophilia care over nearly a century, focusing on the reshaping of clinical practice by extended half-life (EHL) coagulation factors, bispecific antibodies, rebalancing therapies, and gene therapy. She emphasized how to achieve precise personalized medicine through the quality framework of "Structure-Process-Outcome" amidst the current surge of innovative drugs.01 Historical Retrospective: The Lifecycle Leap from an 11-Year Expectancy to Near-Normal
Survival Professor Chowdary pointed out that Hemophilia A and B, as X-linked recessive genetic bleeding disorders, essentially stem from the deficiency of coagulation factor VIII (FVIII) or IX (FIX), leading to impaired endogenous thrombin generation. The history of hemophilia treatment is a history of struggle against disability and death. • Changes in Life Expectancy: According to a cohort study published in 1937, the average life expectancy for hemophilia patients at that time was only 11 years. Today, thanks to the evolution of treatment modalities over the past 50 years (from plasma products and cryoprecipitate to recombinant coagulation factors), patient survival is approaching that of the non-hemophilic population. • Evolution of Treatment Models: The blood safety crisis of the 1980s (HIV/HCV contamination) prompted the birth of recombinant factors. Subsequently, prophylaxis became the standard treatment for severe patients, aiming to convert the severe phenotype into a moderate one. A Dutch nationwide study confirmed that the popularization of prophylaxis significantly reduced bleeding rates and increased the proportion of patients without joint damage. • Unmet Needs: Despite the improvement in survival, traditional prophylaxis (intravenous injections 2-3 times a week) imposes a massive treatment burden, and the development of inhibitors remains a severe challenge during the treatment process.
02 Extended Half-Life (EHL) Factors: Balancing Pharmacokinetics and Treatment Burden
Innovation begins with creating choices. The emergence of extended half-life (EHL) coagulation factors is the first step toward personalized hemophilia treatment. • Technical Differences between FIX and FVIII: o FIX-EHL: Through technologies such as Fc-fusion or PEGylation, the half-life of FIX has been extended by 4-5 fold. Clinically, patients can achieve prophylaxis once a week or even at longer intervals. o FVIII-EHL: Because FVIII is restricted by the metabolism of its carrier protein, von Willebrand factor (VWF), its half-life extension is only approximately 1.5 fold. • Clinical Significance from the Patient’s Perspective: Although the biological extension data for FVIII may seem modest, Professor Chowdary shared a key case: For a doctor, 1.5 times is a pharmacokinetic adjustment; but for a patient, it means 52 fewer intravenous injections per year. This discrepancy in the perception of “treatment burden” is exactly the gap that personalized medicine needs to bridge.
03 Non-factor Therapies: Remodeling the Logic of Thrombin Generation
The rise of non-factor therapies has completely changed the traditional “replace what is missing” model of hemophilia. • Bispecific Antibodies (represented by Emicizumab): o Mechanism of Action: Mimics the function of FVIIIa by bridging FIXa and FX to restore thrombin generation. o Efficacy Data: The amount of thrombin generated by Emicizumab is equivalent to an FVIII level of 15-20 IU/dL. o Clinical Advantages: Subcutaneous administration, low frequency of injection, and effectiveness in Hemophilia A patients both with and without inhibitors. A series of clinical studies (HAVEN series) confirmed its ability to significantly reduce the annualized bleeding rate (ABR), with over 50% of patients achieving zero bleeds. • Rebalancing Therapies: o Core Logic: Targeting anticoagulant pathways. Rebalancing the procoagulant and anticoagulant systems by inhibiting Tissue Factor Pathway Inhibitor (TFPI) or Antithrombin (AT). o Representative Drugs: Fitusiran (siRNA targeting AT), Concizumab (monoclonal antibody targeting TFPI), and Marstacimab. o Applicable Population: These drugs possess “pan-hemophilia” applicability, meaning they can be used via subcutaneous injection for both Hemophilia A and B patients, regardless of inhibitor status.
04 Gene Therapy: Transitioning from Chronic Management to “Clinical Cure”
Gene therapy represents the highest dimension of hemophilia treatment, aiming to achieve stable endogenous expression of FVIII or FIX through a one-time infusion. • Vector Technology: Currently, Adeno-associated virus (AAV) vectors are primarily used due to their non-pathogenicity and high liver tropism. • Hemophilia B Gene Therapy (Etranacogene dezaparvovec): o Clinical Performance: Utilizing the Padua variant FIX gene (which increases activity by approximately 8-fold). Data shows that 5 years after infusion, patients maintain stable and high plateau FIX levels, and the vast majority have discontinued prophylaxis. • Hemophilia A Gene Therapy (Valoctocogene roxaparvovec): o Challenges and Status Quo: Compared to FIX, FVIII gene expression shows a slow downward trend several years later. Nevertheless, in the 5-year follow-up data, 83% of patients remained off prophylaxis. • Safety Considerations: Immune-mediated transaminitis (requiring steroid intervention), potential hepatotoxicity, and integration risks still require support from long-term follow-up data. Professor Chowdary emphasized that gene therapy is not just a product but a complex clinical pathway including preoperative screening (neutralizing antibody testing) and rigorous postoperative monitoring.
05 The Core of Personalized Medicine: Structure, Process, and Shared Decision Making
With a rich “arsenal” available, precise application becomes the core of personalized medicine. Professor Chowdary introduced Donabedian’s quality management framework (Structure-Process-Outcome): • The Value of “Process”: In personalized diagnosis and treatment, the combination of process standardization and flexibility is crucial. For example, evaluating the risk of joint disease through biomarkers or using novel testing methods to assess a patient’s bleeding tendency. • Dynamic Adjustment of Treatment Strategies: o Childhood: Focus is on establishing prophylaxis, reducing injection burden, and protecting joints. o Adolescence / Early Adulthood: Consideration of physical activity levels. For patients engaged in high-intensity sports, prophylaxis regimens providing high peak factor levels are required. o Elderly: Need to consider limited venous access and anticoagulation management for comorbidities (such as cardiovascular disease). • Shared Decision Making (SDM): Personalized medicine is not just a choice of medical technology but a reflection of the patient’s values. Doctors must objectively interpret the risk-benefit ratios of various therapies (e.g., the uncertainty of gene therapy vs. the convenience of factor therapy) and ensure patients make decisions that best align with their life goals through in-depth communication for over 12 weeks (the “Cooling-off Period”).
Conclusion and Future Outlook
Professor Chowdary concluded that hemophilia care is at an explosive stage for personalized medicine. Our therapeutic goal has shifted from “avoiding death” to “zero bleeds,” and finally to “reducing the footprint of hemophilia” on the patient’s life trajectory. • Zero ABR: Should become the minimum standard for prophylaxis. • Equitable Benefit: The success of personalized medicine depends not only on the research and development of high-tech solutions but also on whether the healthcare system can ensure that every patient receives the innovative therapy best suited to their condition in a fair and precise manner.
The future of hemophilia is no longer a “one-size-fits-all” infusion but a deep customization based on genetic background, pharmacokinetics, lifestyle, and personal preferences. In this process, the combination of rigorous clinical evidence and humanistic care will ultimately define the success of hemophilia management.
