UKHCDO gene therapy taskforce: Guidance for implementation of haemophilia gene therapy into routine clinical practice for adults.

Abstract

Introduction: 2022 was a landmark year with two adeno-associated viral vectors (AAVs) receiving conditional marketing authorization from EMA for the treatment of persons with severe haemophilia A and severe to moderately severe haemophilia B and a third in 2024. Gene therapy is a transformative, irreversible treatment with long-lasting effects, necessitating development of new clinical pathways to ensure optimal outcomes.

Aim: To develop a consensus framework and service specification for delivery of AAV gene therapy for haemophilia in adults within the UK using the hub-and-spoke model proposed by the European Association of Haemophilia and Allied Disorders and the European Haemophilia Consortium.

Methods: The UK Haemophilia Centre Doctors Organisation (UKHCDO) set up a working party to develop expert consensus guidance, working with NHS England to ensure alignment with NHS England commissioning and the national service specification.

Results: These guidelines detail the patient pathway, counselling and governance requirements for the hub-and-spoke model. The national service specification requires the hub site to manage governance for AAV-based gene therapy. Proposed regional and national multidisciplinary teams will harmonize clinical practices incorporating expertise from various specialities and professional groups. Key requirements identified include standardized documentation and multidisciplinary collaboration. Nationally agreed patient information and counselling checklists will streamline the informed consent process and facilitate data collection for long-term safety and efficacy monitoring.

Conclusion: These guidelines provide a structured framework for the delivery of liver-directed gene therapy. Whilst specific to the United Kingdom they provide a framework for the implementation of gene therapy in other countries for haemophilia and other monogenic disorders.