The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains 
a major treatment complication encountered in the treatment of haemophilia. Not 
all patients with even the same severity and genotype develop inhibitors 
suggesting an underlying mechanism of tolerance against FVIII- or FIX-related 
immunity. One mechanism may be central tolerance observed in patients in whom 
the FVIII mutation enables some production of the protein. The other is a 
peripheral tolerance mechanism which may be evident in patients with null 
mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI-1, BAX801) 
has been developed for the haemostatic treatment of both congenital haemophilia 
with inhibitor (CHAWI) and acquired haemophilia A (AHA). In 28 subjects with AHA 
with life-/limb-threatening bleeding, rpFVIII reduced or stopped bleeding in all 
patients within 24 h. The cross-reactivity of anti-human FVIII antibodies to 
rpFVIII remains around 30-50%. Recently, new therapeutics based on the quite 
novel concepts have been developed and clinical studies are ongoing. These are 
humanized asymmetric antibody mimicking FVIIIa function by maintaining a 
suitable interaction between FIXa and FX (Emicizumab, ACE910), and small 
interfering RNAs (siRNA, ALN-AT3) suppress liver production of AT through 
post-transcriptional gene silencing and a humanized anti-TFPI monoclonal 
antibody (Concizumab). Their main advantages are longer half-life, subcutaneous 
applicability and efficacy irrespective of the presence of inhibitors which will 
make it easier to initiate more effective treatment especially early childhood.