Abstract
Haemophilia is a rare disease with high morbidity and mortality in its severe form. The mainstay of haemophilia management has been regular prophylactic infusions of the missing coagulation factor (FVIII/FIX) to reduce morbidity and mortality associated with chronic, crippling arthropathy. This approach is burdensome and costly for patients due to the need for frequent intravenous infusions, high costs, limited availability, and the development of inhibitors. Advances in the engineering and manufacturing of clotting concentrates have led to the creation of novel molecules that address many of these limitations. These include the development of extended half-life factors, which require less frequent infusions, and new non-factor replacement treatments that can be administered subcutaneously and infrequently, such as FVIII-mimetic antibodies (e.g., emicizumab) and downregulators of natural anticoagulants (e.g., antithrombin, tissue factor pathway inhibitor, or activated protein C). Finally, gene therapy is set to offer patients the possibility of a cure by transferring a functional copy of the gene required to express the missing or dysfunctional clotting factor. This therapy was approved for the treatment of haemophilia A and B in 2022 in Europe and the United States and is currently in late-phase clinical investigation
