Subcutaneous Treatment Hope: Non-Factor Care in Children with Hemophilia

Hemophilia A or B is an inherited bleeding disorder due to a deficiency of factor VIII or IX. Depending on the severity, bleeding may already occur after birth and in very young patients, e.g., intracranial hemorrhage or bleeding in muscle, soft tissue, and joints during surgery or after little accidents.

Despite great improvements in factor therapy concerning half-life and less frequent injections, remaining issues are the intravenous administration and inhibitor development. Additionally, a primary regular factor prophylaxis maybe more effective to prevent joint bleeds and damages in adolescence and adults.

Non-factor therapies have been a so-called "game changer" in hemophilia care, most of all due to the subcutaneous application and improved quality of life. Existing data demonstrate a more stable coagulation activation and effective bleeding prevention, also in patients with inhibitors. These novel therapies work either as factor mimetics, providing similarity to the missing factor, or they have a rebalancing effect by targeting natural coagulation inhibitors, such as tissue factor pathway inhibitor, or protein C. Depending on data and the approval situation, these therapies may allow an easier and earlier start of prophylaxis and potentially prevent early bleeding. However, concerns about these new treatments include, e.g., risk of coagulation imbalances and insufficient monitoring.

This review will comprise an overview of non-factor treatment, such as FVIII mimetics and re-balancing therapies, including working profile, pediatric data, and approval situation in Europe, Switzerland, and the United States.