Children and Adults With All Types of von Willebrand Disease
Sidonio RF Jr, Boban A, Dubey L, et al. Blood Advances. 2024;8(1):1-13.
Routine prophylaxis is well established as the standard of care in hemophilia—and provides a strong rationale for prophylaxis in managing severe von Willebrand disease (VWD) phenotypes1
Evidence shows that prophylaxis in VWD results in a lower disease burden, fewer spontaneous bleeds and hospitalizations for bleeds; and less chronic pain and chronic joint damage vs on-demand treatment—with a lower risk of iron deficiency and anemia1-4
Updated VWD guidelines from ASH, ISTH, NBDF, and WFH recommend long-term prophylaxis with a von Willebrand factor (VWF) concentrate in adults and children with VWD experiencing severe symptoms5
wilate® is a plasma-derived factor concentrate containing VWF and factor VIII (FVIII) in a physiologic (balanced) 1:1 ratio. wilate is indicated in all types of VWD in patients ≥6 years for treatment of bleeds, perioperative management of bleeding, and most recently approved for routine prophylaxis2
Methodology
Global, prospective, phase 3 trial conducted in 33 adults and children (19 M, 14 F, ≥6 years) with severe VWD – VWD type 1 (n=6), type 2A (n=5), type 3 (n=22)
– More than 25% of participants were younger than 12 years of age; 21% were of child-bearing potential – No history/suspicion of VWF and FVIII inhibitors or history of thromboembolism
wilate prophylaxis: 20-40 IU/kg infused 2 to 3 times per week for 12 months
Primary endpoint: >50% reduction in mean annualized bleed rate (ABR) vs prior on-demand treatment
Additional endpoints: spontaneous ABR, ABR for heavy menstrual bleeds, Pictorial Blood Loss Assessment Chart (PBAC) score for menstrual bleeds, consumption of wilate, treatment-emergent adverse events
All patients enrolled in WIL-31 had completed a prospective, 6-month run-in trial (WIL-29) that collected data on treated (on-demand) bleeds with any available VWF/FVIII concentrate during routine clinical practice
If ≥2 BEs were treated with a VWF-containing product, patients were eligible for WIL-31
ASH, American Society of Hematology; ISTH, International Society on Thrombosis and Haemostasis; NBDF, National Bleeding Disorders Foundation; WFH, World Federation of Hemophilia.
Indications and Usage
wilate® is a von Willebrand Factor/Coagulation Factor VIII Complex (Human) indicated in children and adults with von Willebrand disease (VWD) for on-demand treatment and control of bleeding episodes; for perioperative management of bleeding; and for routine prophylaxis to reduce the frequency of bleeding episodes in children 6 years of age and older and adults with VWD. wilate is also indicated in adolescents and adults with hemophilia A for routine prophylaxis to reduce the frequency of bleeding episodes; and for on-demand treatment and control of bleeding episodes.
Please see enclosed full Prescribing Information.
WIL-31 Study Results
wilate prophylaxis significantly reduced mean total ABR at 12 months by 84% vs prior on-demand treatment—achieving the primary study endpoint
PRIMARY ENDPOINT: Mean change in total ABRs
30% of patients had ZERO total bleeds and 54.5% had ZERO treated spontaneous bleeds
99% of treated BEs were rated by patients as “excellent” (90%) or “good” (9%)
Of 173 BEs that occurred in 23 patients, 84% of bleeds were minor
Most treated BEs (87%) were managed with 1 or 2 infusions
Most patients achieved bleeding control with twice weekly dosing
At study end, 70% of patients received twice-weekly dosing and 30% three times per week dosing
Median (range) weekly dose of wilate for prophylaxis was 58 (28–114) IU/kg
SAFETY & TOLERABILITY: No serious treatment-emergent adverse events related to wilate, no inhibitor formation, and no thrombotic events were detected during 12 months of prophylaxis.
Contraindications
wilate is contraindicated in patients with known hypersensitivity reactions, including anaphylactic or severe systemic reactions, to human plasma-derived products, any ingredient in the formulation, or components of the container.
Warnings and Precautions
Hypersensitivity Reactions
Hypersensitivity reactions may occur with wilate. Signs and symptoms include angioedema, burning and stinging at the infusion site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, and wheezing that may progress to severe anaphylaxis (including shock) with or without fever. Closely monitor patients receiving wilate and observe for any symptoms throughout the infusion period. Because inhibitor antibodies may occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.
wilate prophylaxis significantly reduced mean spontaneous ABR and reduced bleeding across all sites versus prior on-demand treatment
REDUCTION IN BLEEDS
AMONG VWD TYPES 1, 2A, AND 3: Reductions in mean total ABR were 68%, 97%, and 86% Reductions in ABRs were similar across VWD types, age groups, & gender
Warnings and Precautions
Thromboembolic Events
AMONG CHILDREN, ADOLESCENTS, AND ADULTS: Reductions in mean total ABR were 87%, 85%, and 82%
AMONG MALES AND FEMALES: Reductions in mean total ABR were 82% and 87%
In VWD, continued treatment using a FVIII-containing VWF product may cause an excessive rise in FVIII activity, which may increase the risk of thromboembolic events. Monitor plasma levels of VWF:RCo and FVIII activities in patients receiving wilate to avoid sustained excessive VWF and FVIII activity levels.
Neutralizing Antibodies (VWD)
Neutralizing antibodies (inhibitors) to FVIII and VWF in patients with VWD, especially type 3 patients, may occur. If a patient develops inhibitor to VWF (or to FVIII), the condition will manifest itself as an inadequate clinical response.
Thus, if expected VWF activity plasma levels are not attained, or if bleeding is not controlled with an adequate dose or repeated dosing, perform an appropriate assay to determine whether a VWF inhibitor is present.
In patients with antibodies against VWF, VWF is not effective and wilate administration may lead to severe adverse events. Consider other therapeutic options for such patients.
Because inhibitor antibodies may occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.
Routine VWD Prophylaxis
Results of WIL-31 provide compelling evidence supporting broader use of VWF prophylaxis in children and adults with all types of VWD.
Adoption of prophylaxis in VWD has been low. Barriers may include cost, access to intravenous (IV) administration, variable bleeding, perceived lack of efficacy, and lack of awareness. It may also be due to narrow indications of VWF products for prophylaxis, such as Vonvendi®—approved only for adults with type 3 VWD transitioning from on-demand treatment, but not for patients switching from prior prophylaxis or for patients with type 1 or type 2 VWD
In contrast, WIL-31 included patients with VWD who were 6 years of age and older and encompassed a more representative sample of patients across all types of VWD
wilate is the ONLY Available VWF Concentrate Approved for Routine Prophylaxis in All Types of VWD in Children (≥6 Years) and Adults2,6,7,8
Types 1,2,3 VWD patients ≥6 years
3 only
Vonvendi® is a registered trademark of Takeda. Humate-P® is a registered trademark of CSL Behring GmbH. Alphanate® is a registered trademark of Grifols.
and
NOTE: Presentation of Vonvendi®, Humate-P®, and Alphanate® information is not intended to claim or imply inferiority, equivalence, or superiority to wilate in efficacy, safety, or other conditions of use.
For all inquiries relating to drug safety, or to report adverse events, please contact our local Drug Safety Officer: Tel: 201-604-1137 | Cell: 201-772-4546 | Fax: 201-604-1141 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Important Safety Information
Transmissible Infectious Agents
wilate is made from human plasma. Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the variant Creutzfeldt-Jakob disease (vCJD) agent. There is also the possibility that unknown infectious agents may be present in the product. The risk that wilate will transmit viruses has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and removing certain viruses during manufacture. Despite these measures, it may still potentially transmit disease. Record the batch number of the product every time wilate is administered to a patient, and consider appropriate vaccination (against hepatitis A and B virus) of patients in regular/repeated receipt of wilate. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Octapharma USA, Inc., at 1-866-766-4860.
Monitoring and Laboratory Tests
Monitor plasma levels of VWF:RCo and FVIII activities in patients receiving wilate to avoid sustained excessive VWF and FVIII activity levels, which may increase the risk of thromboembolism, particularly in patients with known clinical or laboratory risk factors. Monitor for development of VWF and FVIII inhibitors. Perform assays to determine whether VWF and/or FVIII inhibitor(s) is present if bleeding is not controlled with the expected dose of wilate.
Adverse Reactions
The most common adverse reactions to treatment with wilate (���� ≥ 1%) in patients with VWD were hypersensitivity reactions, urticaria, and dizziness. The most common adverse reactions to treatment with wilate (���� ≥ 1%) in previously treated patients with hemophilia A was pyrexia (fever). Seroconversions for antibodies to parvovirus B19 not accompanied by clinical signs of disease have been observed.
The most serious adverse reactions to treatment with wilate in patients with VWD and hemophilia A are hypersensitivity reactions.
References: 1. Miesbach W, Berntorp E. Thromb Res. 2021;199:67-74. 2. wilate full Prescribing Information. Paramus, NJ: Octapharma; rev December 2023. 3. Sidonio RF, et al. Blood Adv. 2024;8(1):1-13. 4. James P, James AH. VWD: Gynecologic and obstetric considerations. Accessed November 29, 2023. https://www.uptodate.com/contents/von-willebrand-disease-vwd-gynecologic-and-obstetric-considerations 5. Connell NT, et al. Blood Adv. 2021;5(1):301-325. 6. Vonvendi® Prescribing Information. Takeda Pharmaceuticals; March 2023. 7. Humate-P® Prescribing Information. CSL Behring; June 2020. 8. Alphanate® Prescribing Information. Grifols Biologics; March 2021.
