Von Willebrand factor/factor VIII (Wilate) prophylaxis in children aged <6 years with severe von Willebrand disease

Long-term prophylaxis with von Willebrand factor (VWF) concentrate is recommended in individuals with von Willebrand disease (VWD) and a history of severe and frequent bleeding. The efficacy and safety of prophylaxis with the plasma-derived VWF/factor VIII (FVIII) 1:1 concentrate Wilate was demonstrated in adults, adolescents and children aged ≥6 years with VWD of all types in the WIL-31 study, the largest prophylaxis study conducted in VWD to date. However, limited data are available on VWF prophylaxis in children <6 years. The WIL-33 study prospectively investigated the efficacy and safety of 12-month Wilate prophylaxis in children <6 years with severe VWD. Data were analyzed for the full analysis set (FAS, N=12) and a per-protocol robustness (PPR) set (N=9), which excluded three participants with deviations from recommended dosing. The mean (SD) total annualized bleeding rate (TABR; primary endpoint) was 4.6 (6.1) in the FAS and 2.7 (1.8) in the PPR set. Most bleeding episodes (BEs) during prophylaxis were minor (55/56; 98.2%), and all treated BEs were successfully treated with one (95.6%) or two (4.4%) Wilate infusions. Pharmacokinetic parameters of Wilate were within the expected ranges for VWF in young children. One nonserious treatment-emergent adverse event (pyrexia) was assessed as possibly related to study medication. No thromboembolic events or inhibitors to VWF or FVIII developed during the study. Wilate was efficacious and well tolerated in the prevention and treatment of BEs in children <6 years, supporting earlier initiation of VWF prophylaxis in young children with severe phenotypes. WIL-33 was registered at www.clinicaltrials.gov (NCT04953884).