Improvements in factor concentrates

The aim of this review is to highlight strategies being pursued to enhance current concentrate therapies for the hemophilias. During the past 5 years, significant progress has been made with a variety of protein-engineering initiatives, some of which are already in early-phase clinical trials.

The standard of care for hemophilia therapy involves the infusion of clotting factor concentrates either at the time of bleeding (on demand therapy) or in a prophylactic schedule to prevent bleeding episodes. This latter approach to therapy has been used in some parts of Europe for several decades and has recently been shown, in a prospective randomized study, to result in a significant reduction in musculoskeletal pathology. The aim of many of the novel concentrates under development is to prolong the half-life of the infused clotting factor and thus to reduce the frequency of infusions. Several different strategies are being evaluated for this purpose including conjugation with hydrophilic polymers and generation of fusion proteins that are recycled by the FcRn receptor.

The speed of progress with the development of several approaches to extend clotting factor half-lives has been encouraging. It is very likely that several of these concentrates will reach the clinic in the near future.