Issues

State of the art on clinical trials of gene therapy in haemophilia

Haemophilia A and B are rare inherited bleeding disorders, caused by deficiency or dysfunction .of the coagulation factors(F) VIII (haemophilia A) or IX (haemophilia B) which have an essential role in the coagulation cascade. These dysfunctions cause a defect in clot formation and consequent bleeding diathesis. The main therapeutic strategy is the venous infusion of either plasma-derived or recombinant products. Treatment is given in response to an acute bleeding episode (on-demand) or as prophylaxis by infusion 2-3 times per week to prevent haemorrhages.
Nowadays, the introduction of new extended half-life products has transformed the concept of haemophilia replacement therapy by reducing the frequency of injections, achieving a higher trough level and improving patients’ quality of life. Furthermore, a substantial change has happened with the availability of the bispecific antibody. Haemophilia A patients with and without inhibitors can be subcutaneously treated reducing significantly the interval between injections once a week or every two weeks.
In the last few years, clinical trials in both haemophilia A and B hve shown efficacy and durability of transgene expression. Phase 1/2 studies have shown that a single intravenous infusion allows to reach a normal level in patients with haemophilia A and B. Long-term follow-up for gene therapy in haemophilia B showed that the infusion of a single dose of vector resulted in a therapeutic FIX activity level after 10 years. These levels of FVIII and FIX expression allow to patients to leave the prophylactic regimen and to reduce the bleeding events to zero. This article mentions the state of the art of gene therapy studies for haemophilia A and B, including data on efficacy and any side effects observed until now.