Hemlibra for Hemophilia B!?

By Dr. David Clark

7/10/24 

Hemlibra is a treatment for hemophilia A.  It is an antibody that mimics the action of factor VIII by binding to both activated factor IX (FIXa) and factor X to activate the factor X.  It is not indicated for the treatment of hemophilia B, but recent studies show that it might actually be beneficial for a few hemophilia B patients. 

How does that work?  Both factor VIII and Hemlibra bind to FIXa, but at slightly different places on the FIXa molecule.  If the mutation on the factor IX molecule that causes the patient’s hemophilia B is in the area where factor VIII normally binds, that might keep factor VIII from being able to do its job, so the patient bleeds.  However, if the other area on the factor IX molecule where the Hemlibra antibody binds is not affected by the mutation, Hemlibra could still bind to it and then bring that mutated factor IX molecule into contact with factor X to continue the clotting reactions. 

This would only work for the small number of hemophilia B patients who have a mutation that inhibits factor VIII from binding to factor IX, but those patients might benefit from using Hemlibra instead of clotting factor.  Hemlibra is a subcutaneous treatment with a very long half-life, so injections are easier and less frequent.  With more research, doctors may be able to identify the patients who could use Hemlibra, just from the genetic sequence of their factor IX gene.  [Lee K et al., Blood, online ahead of print 7/10/24]