Impact of Emicizumab on Hemophilia Management

Abstract

Hemophilia A is an X-linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII(FVIII) that occurs in approximately 1 in 5,000 male births. Patients with plasma factor activity levels < 1% areclassified as having severe hemophilia. To prevent recurrent joint bleeding, which leads to QOL loss due to severearthropathy, patients need to receive regular intravenous infusions (prophylaxis) of FVIII products. However,there are many concerns regarding 1) the requirement of 2–3 times/week venipuncture for intravenous infusion, 2)frequent visits to the hospital (2–3 times/week in childhood), and 3) one-third of patients with severe hemophiliaA developing anti-FVIII neutralizing alloantibodies (inhibitors) toward the infused factor. Given this, patients andtheir caregivers encounter not only physical stress but also mental and social stress. To resolve these problems,prophylaxis with subcutaneous long-acting nonfactor products that improve in vivo thrombin generation is nowsuccessfully employed in hemophilia patients. These nonfactor products caused a paradigm shift in the treatmentand management of hemophilia. The novel agent emicizumab (Hemlibra®) is a recombinant humanized, bispecificmonoclonal antibody that simultaneously binds to activated factor IX and factor X, thereby mimicking the cofactor function of activated FVIII. Emicizumab has been shown to be safe and effective for the prevention of bleedsin patients with severe hemophilia A, both with and without inhibitors, but it has no indication in hemophilia B.One time/2 or 4 weeks administration was required for maintenance therapy. These benefits contributed by thelong half-life and subcutaneous administration make emicizumab an attractive therapeutic option for prophylaxisin infants with severe hemophilia; however, clinical data to inform treatment decisions in infants are almost absent. As the QOL of hemophilia patients and their caregivers is improved by emicizumab administration, emicizumab might be changed as a mainstream treatment for severe hemophilia in all patients, including infants.