Expanding the Toolbox With Non‐Factor Therapies

Prophylaxis is the standard of care for people living with haemophilia (PwH) as it is able to prevent majority of bleeding episodes, including joint bleeds and life-threatening bleeds (i.e., intracranial haemorrhage). However, despite undeniable advantages, prophylaxis has limitations including need for frequent intravenous infusions and cost. Adherence to long-term treatment regimens based on multiple weekly intravenous injections of standard half-life products is challenging, and it is highly likely that injections are skipped or delayed with great impact on efficacy due to the rather rapid clearance of the drug from the body. The advent of extended half-life products allowed for greater flexibility and easier treatment personalization with the possibility to improve protection as well as to reduce number of intravenous injections. For people living with haemophilia A and inhibitors the advent of the first non-replacement therapy, emicizumab, made a turning point offering for the first time an effective prophylaxis with the additional advantage of a consistent steady state of haemostatic effect across different ages and body weights and of subcutaneous route of administration. However, during emicizumab prophylaxis breakthrough bleeds might occur due to the limited haemostatic potential which stays in the mild haemophilia range with some interindividual variability and not clearly definable FVIII equivalence. More recently the toolbox for haemophilia care has further expanded with several non-factor therapies that will offer the opportunity of effective prophylaxis to people with haemophilia B with inhibitors, subcutaneous prophylaxis for all PwH and the promise of protection in the non-haemophilia range.