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

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