Hemophilia and von Willebrand disease are the most common congenital bleeding 
disorders. Treatment of these disorders has focused on replacement of the 
missing coagulation factor to prevent or treat bleeding. New technologies and 
insights into hemostasis have driven the development of many promising new 
therapies for hemophilia and von Willebrand disease. Emerging bypass agents 
including zymogen-like factor IXa and Xa molecules are in development and a 
bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in 
people with hemophilia A and inhibitors. Tissue factor pathway inhibitor, the 
protein C/S system, and antithrombin are targets of novel compounds in 
development to alter the hemostatic balance and new approaches using modified 
factor VIII molecules are being tested for prevention and eradication of 
inhibitor antibodies in hemophilia A. The first recombinant von Willebrand 
factor (VWF) product has been approved and has unique VWF multimer content and 
does not contain factor VIII. These new approaches may offer better routes of 
administration, improved dosing regimens, and better efficacy for prevention and 
treatment of bleeding in congenital bleeding disorders.