The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing

Summary

Congenital haemophilia A (factor VIII deficiency) and B (factor IX deficiency) are X-linked bleeding disorders. Replacement therapy has been the cornerstone of the management of haemophilia, aiming to reduce the mortality and morbidity of chronic crippling arthropathy. Frequent intravenous injections are burdensome and costly for patients, consequently with poor adherence and restricted access to therapy for many patients worldwide. Bioengineered clotting factors with enhanced pharmacokinetic profiles can reduce the burden of treatment. However, replacement therapy is associated with a risk for inhibitor development that adversely affects bleeding prevention and outcomes. Novel molecules that are subcutaneously delivered provide effective prophylaxis in the presence or absence of inhibitors, either substituting for the procoagulant function of clotting factors (eg, emicizumab) or targeting the natural inhibitors of coagulation (ie, antithrombin, tissue factor pathway inhibitor, or activated protein C). The ultimate goal of haemophilia treatment would be a phenotypical cure achievable with gene therapy, currently under late phase clinical investigation.