Italian Patients Journey for Gene Therapy in Haemophilia A

Introduction: Gene therapy (GT) provides sustained FVIII levels without repeated infusions in Hemophilia A (HA) patients thus overcoming a major limitation of replacement therapy. However, issues remain e.g., patient selection criteria, duration and variability of transgene expression, quality of life and long-term safety. Aim: This expert opinion guidance aims to define the optimal operational pathway and organizational model in Italy for the approved gene therapy (GT) product valoctocogene roxaparvovec, for patients with HA. Methods: A multidisciplinary Working Group (healthcare professionals experienced in managing patients with HA and representatives of patients' Associations) critically analysed the Summary of Product Characteristics (SmPC) of valoctocogene roxaparvovec and some key publications concerning GT in haemophilia. The emerging evidence, alongside with the Working Group member expertise, helped to develop this journey for Italian patients with HA treated with this AAV5-FVIII based GT. Results: The present journey is divided into five sections: selection and screening of eligible patients, GT prescription, GT administration and post-infusion (short-term [≤1 year] and long-term [>1 year-up to 15 years] post-GT follow-up). Each phase involves collaboration between centres organized in a Hub and Spoke model, adoption of Shared Decision Making (SDM) approach, multidisciplinary team working and national data collection. Conclusion: This product-specific operational pathway proposal provides Italian clinicians with a comprehensive framework for managing patients with HA treated with GT, acknowledging the evolving nature of this innovative therapy and the need for continuous evaluation of the proposed pathway. The present journey may need adaptation for other GT products.