The US Food and Drug Administration has expanded the indication for recombinant von Willebrand factor (VWF), marketed as Vonvendi, to include pediatric patients with von Willebrand disease (VWD) for both acute bleeding episodes and perioperative use. The September 5, 2025 approval establishes recombinant VWF as the first non-plasma-derived therapy available for pediatric patients with VWD in the United States.
The expanded approval also extends routine prophylactic use to adults with all types of VWD, broadening the previous indication that was limited to adults with severe Type 3 VWD receiving on-demand therapy.
Regulatory Milestone for Rare Disease Treatment
"This approval demonstrates FDA flexibility in evaluating applications of therapeutics to treat rare diseases," said Vinay Prasad, MD, MPH, director of the FDA's Center for Biologics Evaluation and Research. "When we see the trifecta of plausible mechanism of action, robust pharmacology/biologic science, and supportive clinical study data, we promptly act even if that data is derived from a small sample size study."
The decision represents the fourth FDA approval for recombinant VWF over the past decade. The therapy initially received approval in December 2015 for treating bleeding episodes in adults with VWD based on two trials enrolling 69 patients. Subsequent approvals came in 2018 for perioperative bleeding management in adults following a multicenter phase 3 study, and in 2022 for prophylactic use in adults with severe Type 3 VWD.
Clinical Evidence Supporting Pediatric Use
According to Takeda Pharmaceuticals, the pediatric approval is supported by data from three clinical studies, including a phase 3 trial specifically enrolling children and a phase 3b continuation study that included both children and adults. Real-world evidence also contributed to the expanded indication.
Trial results demonstrated that most non-surgical bleeds in pediatric patients were effectively managed with a single infusion. The therapy showed a reported half-life of 14.3 hours in children compared with 22.6 hours in adults, indicating age-related pharmacokinetic differences that inform dosing strategies.
Clinical Impact for Pediatric Hematology
"Today's approval is a testament to the collaborative interactions between CBER review teams and product developers, aimed at making innovative therapies available for use in pediatric populations, at the same time as adults," said Vijay Kumar, MD, acting director of the CBER Office of Therapeutic Products.
For pediatric hematologists, this approval introduces a recombinant alternative to plasma-derived VWF products, offering more consistent pharmacokinetics and eliminating risks inherent to plasma-based therapies. While prophylaxis remains limited to adults at this time, children with VWD now have access to recombinant therapy for acute management and surgical settings.
Prophylactic Treatment Expansion
The approval also represents a significant advancement for adult VWD management by extending prophylactic use beyond Type 3 patients to all VWD subtypes.
"The FDA's approval of Vonvendi for routine prophylactic use in adults with all VWD types marks a pivotal milestone in advancing care for this challenging condition," said trial investigator Jonathan C. Roberts, MD, associate medical and research director at the Bleeding and Clotting Disorders Institute and associate professor of pediatrics and medicine at the University of Illinois College of Medicine at Peoria. "Establishing prophylaxis as the standard of care for all adults with VWD, regardless of subtype, represents a significant step forward in helping to manage bleeding risk and the burdens that bleeds can have on patients' daily lives."
According to Takeda, recombinant VWF is the only non-plasma-derived VWF product approved for VWD in the United States, providing clinicians with a therapeutic option that eliminates the variability and potential risks associated with plasma-derived products while offering predictable pharmacokinetic properties across patient populations.
