Gene therapy in haemophilia: literature review and regional perspectives for Turkey

Abstract

Haemophilia is an X-linked lifelong congenital bleeding disorder that is caused by insufficient levels of factor VIII (FVIII; haemophilia A) or factor IX (FIX; haemophilia B) and characterized by spontaneous and trauma-related bleeding episodes. The cornerstone of the treatment, factor replacement, constitutes several difficulties, including frequent injections due to the short half-life of recombinant factors, intravenous administration and the risk of inhibitor development. While extended half-life factors and subcutaneous novel molecules enhanced the quality of life, initial successes with gene therapy offer a significant hope for cure. Although adeno-associated viral (AAV)-based gene therapy is one of the most emerging approaches for treatment of haemophilia, there are still challenges in vector immunogenicity, potency and efficacy, genotoxicity and persistence. As the approval for the first gene therapy product is coming closer, eligibility criteria for patient selection, multidisciplinary approach for optimal delivery and follow-up and development of new pricing policies and reimbursement models should be concerned. Therefore, this review addresses the unmet needs of current haemophilia treatment and explains the rationale and principles of gene therapy. Limitations and challenges are discussed from a global and national perspective and recommendations are provided to adopt the gene therapies faster and more sufficient for the haemophilia patients in developing countries like Turkey.