Table 2.

Summary and comparison of novel therapies discussed, outlining mechanism of action, route and frequency of administration, advantages, limitations, and the current licensing status

Therapy	Mechanism of action	Route of administration	Frequency of administration	Advantages	Limitations	Licensing status
Emicizumab	Bispecific antibody mimicking co-factor function of FVIII	Subcutaneous	Once a week, Twice a week, or Monthly	Can be used in patients with FVIII-inhibitors No need for peripheral venous access Reduced frequency of administration Reduced cost of treatment No need for routine laboratory monitoring, practical to use Good safety profile	Interferes with the assays used in laboratory monitoring Insufficient to treat large bleeds on its own, additional haemostatic measures required	Licensed for use in HA patients with and without inhibitors
Fitusiran	GalNAc-siRNA conjugate	Subcutaneous	Once monthly	Application in both HA and HB patients with and without inhibitors Reduced frequency of administration No need for peripheral venous access Good safety profile	More research required for dose selection and management of breakthrough bleeds Lack of paediatric trial data	In phase III of development
Concizumab	Anti-TFPI monoclonal antibody	Subcutaneous	Once daily	Application in both HA and HB patients with and without inhibitors No need for peripheral venous access Good safety profile Improvement in patient QoL	Daily administration Further research required into therapeutic monitoring Further research required into implications for surgery	In phase III of development
Gene therapy	Transduction of a gene coding for deficient factor into patient hepatocytes	Intravenous	Single dose	Application in both HA and HB patients Reduced frequency of administration Improvement in patient QoL Potential role for immune tolerance induction	Lack of long-term follow up Further investigations required into a wider range of patient demographics Potential for degradation by anti-capsid antibodies Diminishing efficacy over time	Undergoing clinical trials

FVIII factor VIII; HA haemophilia A; GalNAc-siRNA N-acetylgalactosamine-small interfering RNA; HB haemophilia B; TFPI tissue factor pathway inhibitor; QoL quality of life