Clinical Evidence and Safety Profile of Emicizumab for the Management of Children with Hemophilia A

Abstract

Emicizumab is a bispecific, humanized, monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the generation of FXa by FIXa in patients with hemophilia A (HA). This subcutaneous non-factor agent has been recently extensively approved for the prophylaxis of patients of HA patients with and without FVIII-inhibitors of all ages, although few data are currently available in children. In Phase 3 clinical trials and case series, emicizumab prophylaxis significantly reduced bleeding rates compared to previous treatment in HA adolescents and children with or without FVIII-inhibitors and was generally well tolerated. In addition, subcutaneous administration of emicizumab provided beneficial effects on health-related quality of life, and lessened the burden of the disease in HA patients as well as in their caregivers. However, additional prospective studies are required to evaluate the long-term safety of emicizumab prophylaxis in very young patients, including previously untreated patients. The aim of this paper was to review the limited data available on the use of emicizumab prophylaxis in children and to highlight the need for further studies to address remaining concerns.

Keywords: emicizumab; factor VIII; hemophilia A; inhibitors; prophylaxis; subcutaneous.

Figure 1

Comparison of pharmacokinetic and efficacy data for each dosing regimen of emicizumab prophylaxis, obtained across the various HAVEN studies. (A) Pharmacokinetic data in adult adolescents patients; (B) Pharmacokinetic data in children; (C) Efficacy data (all ABR) in adult and adolescents patients; (D) Efficacy data (all ABR) in children. QW: 3 mg/kg/week loading dose and 1.5 mg/kg/week maintenance dose; Q2W: 3 mg/kg/week loading dose and 3 mg/kg every 2 weeks; Q4W: 3 mg/kg/week loading dose and 6 mg/kg every 4 weeks; *adult and adolescent patients with severe HA without FVIII-inhibitors; **adult and adolescent patients with severe HA with and without FVIII-inhibitors.