Inhibitor Development in Hemophilia A Patients
Factor VIII (FVIII) replacement is the preferred and most effective therapy for treating Hemophilia A (HA). All newly diagnosed HA patients are treated with this first line therapy. Most Caucasian HA patients are able to continue treatment with replacement FVIII. Unfortunately, about 25% of Caucasian HA patients and half of African American HA patients develop a serious, adverse immune reaction to replacement FVIII. HA patients of African ancestry are especially vulnerable to developing anti-FVIII antibodies and to experiencing markedly poorer outcomes in response to HA therapy than HA patients who are not of African ancestry. The immune reaction creates antibodies to the FVIII replacement protein which that block its activity in the clotting cascade.
The antibodies developed by such patients are often called “inhibitors” and patients who experience this adverse reaction, which renders FVIII ineffective for them, are referred to as “inhibitor patients.”
The development of inhibitors usually happens relatively soon after treatment begins with replacement FVIII. Most HA patients probably make some antibodies to replacement FVIII that are short lived, or do not interfere with the function of their replacement FVIII. Inhibitor patients with HA make what are called neutralizing antibodies. These antibodies do not go away and prevent replacement FVIII from controlling bleeds. Inhibitor patients have substantially more difficulty coping with HA and a much less favorable, long-term prognosis than HA patients who lack inhibitors.
The onset of an inhibitor creates undue hardship on inhibitor HA patients and their families. In addition, the costs of care and treatment of inhibitor patients are an order of magnitude more per year than care for other HA patients. HA patients, their families, and the larger community all stand to benefit from a reduction in the number of HA patients who develop inhibitors in the first place; or from efficient therapies to eliminate anti-FVIII antibodies in any HA patient in which inhibitors emerge. Haplomics is working on developing both safer replacement FVIII products, designed to be less likely to provoke inhibitors and strategies to eliminate anti-FVIII antibodies in inhibitor patients.