Gene therapy for haemophilia in 2023

The cloning of factor VIII (FVIII) and FIX genes in the 1980s allowed several clinical advances such as the genotyping of hemophilia patients, the development of recombinant FVIII and FIX molecules for the treatment of hemophilia and now gene therapy. Valoctocogene roxaparvovec and etranacogen dezaparvovec are the first gene therapy molecules for the treatment of hemophilia A and B respectively, which have obtained regulatory approvals, one in Europe and the other in the United States. There are other gene therapy molecules in the pipelines of the industry and other therapeutic approaches based on gene therapy such as gene editing are under development. The recent clinical trials on gene therapy molecules using adeno-associated virus (AAV) as carrier for FVIII or FIX genes, show clinical efficacy of gene therapy for at least 5 years after a single administration of an AAV vector whose potential liver toxicity requires careful clinical and laboratory monitoring of patients during the first year of the treatment. An asymptomatic increase in alanine aminotransferase is commonly observed in the first 12 months after gene transfer and immunosuppressive treatment, most often with corticosteroids, may be necessary. The evolution of knowledge is currently very rapid in this fascinating scientific field and the national organization to be put in place is a challenge to be met for the national haemophilia reference center. Clinical experience is very limited and patients should benefit from this innovative therapy in a safety framework guaranteed by a multidisciplinary approach involving many specialists like haematologists, hepatologists, psychologists and pharmacists.