Future directions in hemostasis: normalizing the lives of patients with hemophilia

Abstract

The ultimate goal of hemophilia research is to cure the disease by permanently replacing the abnormal or deficient clotting factor. The most promising current approach is to insert a functional gene into the patient that will lead to the production of either the native protein or a compatible non-immunogenic equivalent version. This protein will circulate at adequate levels to prevent spontaneous bleeds and to treat traumatic hemorrhage. While there continues to be progress in this area, there remain significant hurdles to allow the process to be done at minimal risk to the patient. In the short term the goals are: 1) to prevent spontaneous bleeding whenever possible through the provision of effective prophylactic therapy, and 2) to rapidly establish hemostasis when bleeding occurs via effective, safe and widely available treatment modalities. In addition, all therapy should be convenient and simple to use so as to allow the vast majority of hemophilia patients to routinely treat themselves. Optimally, such treatment should not require highly trained medical personnel or vascular access. Prophylactic therapy will be facilitated via the development and introduction of clotting factors with prolonged circulating times. Long acting versions of rFVIIa, rFVIII and rFIX are either already in or are about to enter clinical trials. Rapid treatment of bleeding could be facilitated by bio-engineered molecules with increased activity and/or altered binding characteristics. At least one such agent is in phase II clinical trials. Ease of administration may be accomplished by the introduction of room temperature stable products and the development of subcutaneous and even orally administered therapeutics. It is conceivable that a broad spectrum hemostatic agent capable of normalizing thrombin generation in a variety of deficiencies could be developed. If this is accomplished, the steps to a room temperature stable agent, contained within a pre-filled pen, capable of self-delivery by subcutaneous injection are already within the realm of current developmental capabilities.