Building safeguards for gene therapy in haemophilia

Haemophilia care has progressed through successive therapeutic revolutions, from plasma-derived and recombinant factor replacement to extended half-life products and non-factor therapies. The introduction of gene therapy, with currently approved approaches using adeno-associated viral vectors to deliver functional copies of the factor VIII or IX gene into hepatocytes, now represents the next paradigm shift: a one-time, irreversible intervention designed to restore endogenous factor production. Although early results are promising, the experience of transfusion transmitted infections reminds the haemophilia community that innovation must be matched by vigilance, transparency, and accountability. This Viewpoint examines the ethical and practical safeguards required to ensure the safe and equitable implementation of gene therapy. Five interconnected pillars are outlined: communication and consent, emphasising iterative, transparent, and voluntary decision-making; surveillance and lifelong follow-up, recognising that unknown long-term risks might emerge years after treatment; global registries, such as the World Federation of Hemophilia Gene Therapy Registry, to enable coordinated data collection and real-time safety monitoring; industry accountability, ensuring sustained partnership, transparent data stewardship, and rigorous investigation of safety signals; and ethical and regulatory frameworks, mandating extended monitoring, equity in access, and no-fault compensation mechanisms. As next-generation technologies-including novel adeno-associated virus capsids, lentiviral vectors, and genome-editing approaches-enter clinical development, these principles are essential. The promise of gene therapy must advance with vigilance shaped by history's lessons to sustain public trust and safeguard the future of haemophilia care.