A recently published review has focused on the evolution of treatment landscape of hemophilia A and B, two monogenetic bleeding disorders (coagulation factor VIII and IX deficiency) treated with systemic protein replacement therapy up to the last ten years. Now, several drugs, ranging from antibody to gene to RNA therapy, are transforming this treatment. Replacement therapy with standard half-life products requires twice to thrice weekly intravenous infusions of factor. Extended half-life products may reduce the frequency of injections. Novel non-replacement and gene treatments are under development, at different stages. A recently approved factor VIII-mimetic antibody accomplishes hemostatic correction in patients both with and without inhibitors. Antibodies against tissue factor pathway inhibitor (TFPI) and antithrombin-specific small interfering RNA (siRNA) interfere with natural anticoagulant pathways to rebalance hemostasis. Adeno-associated virus (AAV) gene therapy provides lasting clotting factor replacement and can also be adopted to induce immune tolerance. Gene-editing techniques are currently under clinical or preclinical investigation.
Reference:
Mol Ther. 2019 Nov 13. pii: S1525-0016(19)30502-7. doi: 10.1016/j.ymthe.2019.11.006.