Hemophilia

Hemophilia is a rare but serious bleeding disorder that results from a genetic or an acquired deficiency of a protein required for normal blood coagulation, such as factor VIII (hemophilia A) or factor IX (hemophilia B). The disease varies in severity depending on the extent of residual activity for the deficient factor that can be detected in the circulation of individual patients. Hemophilia patients suffer from both spontaneous bleeding episodes as well as substantially prolonged bleeding times upon injury that can become life threatening. In cases of severe hemophilia, spontaneous bleeding into muscles or joints is frequent and often results in permanent, disabling joint damage.

Hemophilia patients are initially treated by replacement therapy, receiving purified versions of the clotting factor for which they are deficient. However, a significant fraction of hemophilia A patients develop inhibitory antibodies against factor VIII and therefore become refractory to treatment with this factor. These inhibitor patients are then treated with factor VIIa (NovoSeven), an enzyme that can both initiate blood clotting and, at high doses, “bypass” the factor VIII dependent step in coagulation. However, administration of multiple doses of normal factor VIIa (NovoSeven) is often required to control bleeding episodes. In pivotal clinical trials, patients required, on average, approximately three doses over an approximately four hour time period. Sales of NovoSeven are projected to reach $1 B in 2007.

Catalyst’s lead compound, an improved rhFVIIa for treatment of hemophilia, is in development. Catalyst's approach focuses on design of a molecule that combines higher clot-generating activity targeted to the site of bleeding and improved duration of action in vivo. We anticipate that both lower and fewer doses of the improved factor VIIa will be required to control acute bleeding episodes. Catalyst plans to file an IND for clinical testing of an improved Factor VIIa variant in early 2009.