Therapies engineered to prolong
clotting factor protein circulation time, manipulate the balance of pro-
coagulant and anti-
coagulant proteins, or introduce new genetic material to enable endogenous factor
protein production dominate the clinical trial landscape of
hemophilia. The availability of
clotting factor concentrates and the establishment of primary prophylaxis have dramatically improved health outcomes for
hemophilia patients. But, the burden of
hemostatic therapy remains significant, and many barriers to consistent longitudinal use of prophylaxis exist. Several types of emerging
therapeutics including engineered factor concentrates, substitutive
therapies, rebalancing
therapies, and gene transfer/editing all aim to reduce the challenges of current
hemophilia treatment. Emerging treatment options may reduce treatment frequency or need for
intravenous administration. They may also introduce new challenges in laboratory assessment of hemostasis. These novel
therapies must not introduce significant new health risks and continue to support similar or improved outcomes. The potential ramifications of rebalancing the coagulation cascade, particularly in a stress or inflammatory state, or introduction of new genetic material are not trivial. The focus of this review is to provide an overview of active and recently completed clinical trials as well as emerging preclinical data investigating new therapeutic possibilities for
hemophilia patients and potentially other rare
bleeding disorders.