Prophylaxis With von Willebrand Factor VIII Reduces Bleeding in Children, With Akshat Jain, MD, MPH

Prophylaxis with a plasma-derived von Willebrand factor VIII (pdVWF/FVIII) concentrate efficaciously reduces bleeding in patients <6 years with von Willebrand disease (VWD), according to the WIL-33 study.1

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by Akshat Jain, MD, MPH, the medical director of the pediatric and young adult program for hemostasis/thrombosis and sickle cell disease at Loma Linda University Children’s Health, these data fill a gap in VWD care. A prior study, WIL-31, demonstrated the efficacy and safety of pdVWF/FVIII in a 1:1 activity ratio in adult, adolescent, and child patients aged ≥6 years. Prior to WIL-33, however, very little data was available for prophylaxis with VWF in patients <6 years with severe VWD.1,2

“Whenever a clinician is faced with a person with such a severe bleeding disorder, the challenge of guidance on how to treat that patient, how to monitor them, is always there,” Jain told HCPLive in an exclusive interview. “Through this truly global trial, with sites across Asia, Africa, Europe, and North and South America, we’ve truly created a global database.”

WIL-33 was an open-label, non-controlled, international, multicenter, prospective phase 3 study investigating the efficacy, immunogenicity, and safety of pdVWF/FVIII prophylaxis and pharmacokinetics in patients <6 years with severe VWD, defined as VWF ristocetin cofactor activity (VWF;RCo) <20%. pdVWF/FVIII was given at a dose of 30-50 international units (IU) per kg over 12 months, 2-3 times per week. The primary endpoint was total annualized bleeding rate (TABR) during prophylaxis, while safety and tolerability were assessed throughout the study.1

A total of 12 patients were ultimately enrolled in the trial. Baseline median age was 2 years (range, 1-5), 4 patients (33.3%) had VWD type 2, and 8 patients (66.7%) had VWD type 3. The per-protocol robustness (PPR) set, a subset of the full analysis set (FAS), excluded 3 patients due to deviations from recommended dosing. The mean TABR in the FAS and PR set was 4.6 (standard deviation [SD] 6.1) and 2.7 (1.8), respectively. Mean TABR was 2.1 (1) and 5.8 (7.2) in patients with VWD type 2 and VWD type 3, respectively.1

Of 56 total bleeds, >1/3 (22/56; 39%) during prophylaxis in the FAS set were attributed to allergic rhinitis in 1 patient. Mean spontaneous ABR was 0.9 (1.2) in the FAS and 1 (1.3) in the PPR set. The median weekly prophylactic dose was 100 (range, 63-311) and 92 (63-130) IU/kg in the FAS and PPR set, respectively.1

Investigators also noted that pharmacokinetic parameters were within the expected ranges. The mean VWF;RCo half-life was 11.7 hours. All 45 bleeds treated with pdVWF/FVIII during the prophylaxis period in 10/12 patients in the FAS group were managed successfully. Epistaxis was the most common bleed type across patients, while only 1 joint bleed was observed during the study. Additionally, most bleeds (95.6%) only required 1 infusion.1

“I’m really hopeful that our body of evidence will help impact research for the next 5-10 years to come, and we certainly plan on building upon the work we have done by increasing the cohort size and having a more detailed long-term safety profile in the real world,” Jain said. “Hopefully, these data will be shared at the next meeting.”

Editor's Note: Jain reports disclosures with Hemex Health, Sanofi, NovoNordisk, Blue Bird Bio, and Beam Therapeutics.

References

1. Jain A, Leissinger C, Vdovin V, et al. Plasma-derived VWF/FVIII prophylaxis in children under 6 with VWD: First results from wil-33. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Sidonio RF Jr, Boban A, Dubey L, et al. von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease. Blood Adv. 2024;8(6):1405-1414. doi:10.1182/bloodadvances.2023011742