The WFH Guidelines for the Management of Haemophilia: AAV Gene Therapy, 2025

Summary As AAV gene therapy becomes more widely used in clinical practice, evidence-based guidelines with careful interpretation of the evidence by experts are essential to ensure patient safety, standardize clinical practices, address long-term uncertainties, support informed and shared decision-making and build stakeholder trust. This is the first iteration of the WFH Guidelines for the Management of Haemophilia: AAV Gene Therapy. These guidelines were developed to provide comprehensive, evidence-based recommendations to support standardized, safe and effective implementation of gene therapy for haemophilia. They were developed by the WFH AAV Gene Therapy Panel, which is composed of gene therapy experts who were involved in clinical trials and healthcare teams currently treating patients who have received gene therapy, as well as people with haemophilia and their caregivers. Because evidence is rapidly evolving in the treatment landscape for haemophilia, particularly AAV gene therapy, these guidelines have been developed under the WFH LGM, and will be updated as new evidence becomes available. As treatment with AAV gene therapy for haemophilia becomes more common, multiple stakeholders must work together to ensure a seamless and standardized implementation that prioritizes patient safety. Therefore, these guidelines have recommendations for haemophilia treatment centres, the comprehensive care medical team and people with haemophilia. Other stakeholders who may find these guidelines relevant are payors, policymakers, local governments, patient advocacy organizations and drug manufacturers. These guidelines were reviewed by external parties of interest and have been endorsed by the European Haemophilia Consortium (EHC), the Coalition of the Americas, the Council of Ministers of Health of Central America and the Dominican Republic (COMISCA), and the Medical and Scientific Advisory Council (MASAC) of the National Bleeding Disorders Foundation. WFH Guidelines Disclaimer The World Federation of Hemophilia (WFH) does not endorse any treatment product or manufacturer; any reference to a product name is not an endorsement. The WFH does not engage in the practice of medicine and under no circumstances recommends specific products or treatment types for individuals. Guidelines are intended for general information only and are based on population-level research. Guidelines do not replace professional medical care, physician advice or product insert information, but should be used to educate and inform shared decision-making between patients, caregivers and healthcare providers. Furthermore, guidelines may not be complete or accurate because new research studies may have been published or treatments, devices or indications approved after the cut-off date for inclusion in this guideline. Through a comprehensive and systematic literature review, the WFH evidence-informed clinical practice guidelines incorporate data from the existing peer-reviewed literature. Although this literature met the pre-specified inclusion criteria for the guideline, and the WFH considered this scientific content to be the best evidence available for general clinical information purposes at the time the guidelines were developed, this evidence is of varying quality and varying methodological rigour. The WFH and its officers, committees, members, employees, volunteers, guideline authors and reviewers (‘WFH Parties’) disclaim all liability for the accuracy or completeness and disclaim all warranties, express or implied. The WFH Parties further disclaim all liability for any damages whatsoever (including without limitation, direct, indirect, incidental, punitive or consequential damages) arising out of the use, inability to use, or the results of the use of a guideline, any references used in a guideline, or the materials, information, or procedures contained in a guideline, based on any legal theory whatsoever and whether or not there was advice on the possibility of such damages. Haemophilia is a rare X-linked congenital bleeding disorder characterized by a deficiency of coagulation factor VIII (FVIII) in haemophilia A or factor IX (FIX) in haemophilia B. The standard of care for severe haemophilia A and B is regular prophylactic treatment that is aimed at preventing bleeding (See Chapter 6: Prophylaxis in Hemophilia from the third Edition [1]). Despite the development of therapies beyond standard-half-life clotting factor concentrates, several challenges remain for those on prophylaxis. These challenges include high treatment burdens, breakthrough bleeds, progressive joint damage and impaired quality of life [2]. Gene therapy offers the haemophilia community an opportunity to overcome these unmet needs. 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