Hemophilia is a rare hereditary, recessive X-linked, hemorrhagic disorder characterized by deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B). A typical presentation of this disease is spontaneous or traumatic bleeding. Although bleeding can occur in any part of the body, the most frequently affected parts are the joints and muscles. Bleeding into the joints (hemarthrosis) can lead to stiffness, pain, swelling and severe joint damage which can cause the patient severe long-term disability and potentially death if untreated. A while ago, prophylaxis with factor concentrates started at an early age in children with severe or moderate hemophilia, has proven its efficacy over on demand treatment in minimizing the hemorrhagic risk and so the long-term sequelae. Subsequently, after the introduction of extended half-life factor concentrates, patients are living longer and ‘’better’’ as a result of safer factor concentrates, and less treatment burden on young patients.

Despite the great efforts of clinical research, until recently there were no treatments other than replacement factors. Lately, “non-factor therapies” gained their place in the treatment armamentarium of hemophilia. Those are medications that improve hemostasis without replacing the missing factor. These therapies are all designed to be given subcutaneously and at relatively infrequent intervals and thus reducing the treatment burden.

The aim of our presentation is to shed the light on different families of “non-factor therapies”: bispecific monoclonal antibody like emicizumab (approved and available to clinicians for the subcutaneous treatment of hemophilia A) and MIM8 (under investigation), rebalancing agents like fitusiran (an antithrombin inhibitor) and the anti-TFPI (Tissue Factor Pathway Inhibitor) antibodies, as marstacimab or concizumab.