Efficacy and safety of recombinant von Willebrand factor in on-demand treatment of children with von Willebrand disease: up to 4 years of phase 3/3b follow-up.

BACKGROUND: Recombinant von Willebrand factor (rVWF) is approved to treat von Willebrand disease (VWD) in adults and was recently approved in the United States for pediatric on-demand and perioperative treatment. OBJECTIVES: To evaluate the efficacy and safety of rVWF, without or with recombinant factor VIII (rFVIII), for on-demand treatment of bleeding events (BEs) in pediatric patients with VWD. METHODS: A prospective, open-label, phase 3 study (NCT02932618) evaluated efficacy and safety of on-demand rVWF, without or with rFVIII, for treating nonsurgical BEs (for up to 18 months) in patients aged <18 years with severe VWD (VWF:ristocetin cofactor <20 IU/dL). The primary end point was treatment success (mean efficacy, <2.5; 4-point scale, 1 [excellent] to 4 [none]). Patients completing the study could enter a phase 3b continuation study (NCT03879135), evaluating safety and efficacy of rVWF for 3 additional years. RESULTS: Of 25 patients in the phase 3 study, 11 (44%) had type 3 VWD. Eighteen patients reported 104 BEs treated with on-demand rVWF; all were treated successfully (mean [SD] efficacy, 1.01 [0.04]). All 98 BEs with efficacy ratings were rated excellent or good. Most BEs (82%) were treated with 1 rVWF infusion; 27% were treated with additional rFVIII. rVWF was well tolerated, with no adverse events leading to study or treatment discontinuation. No thromboembolic events, severe hypersensitivity reactions, or treatment-related serious adverse events occurred. No neutralizing or binding antibodies to rVWF were observed. Efficacy and tolerability of on-demand rVWF were maintained in the continuation study. CONCLUSION: rVWF, without or with rFVIII, was efficacious for treating nonsurgical BEs in pediatric patients with severe VWD, with efficacy maintained for up to 4 years and no new safety findings.