Vonvendi (vonicog alfa) / Takeda - LARVOL DELTA

Comparative analysis of prophylaxis with 1:1 ratio pdVWF/FVIII concentrate vs. recombinant VWF in type 3 von willebrand disease adults in the United States: Clinical and economic perspective (ASH 2025) - P3 | "In the United States (U.S.), plasma-derived VWF/FVIII (pdVWF/FVIII; wilate®) and recombinant VWF (rVWF; Vonvendi®) are the only two VWF concentrates approved forroutine prophylaxis in VWD. Based on current prophylaxis regimens and U.S. pricing, pdVWF/FVIIIdemonstrates favorable economic value. These findings support its consideration as a cost-saving, first-line prophylactic option in this population."

Clinical • Hemophilia

On 13 November 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Veyvondi. (European Medicines Agency) - "Treatment of haemorrhage in children (aged less than 18 years) with von Willebrand disease (VWD), when desmopressin (DDAVP) treatment alone is ineffective or contraindicated."

CHMP • Hematological Disorders

FVIII and VWF PK: Key Aspects in Safety and Efficiency of VWF Concentrates. Review and Reflection (ASH 2024) - P3 | "These VWFCs are of plasma origin, with one recombinant origin, rVWFC (Vonvendi®), containing only VWF. Among the plasma-derived ones, we have plasma derived Von Willebrand Factor Concentrate with FVIII (pd-VWFC) (Wilate®) with a VWF/FVIII ratio of 1 : 1, and other pd-VWFC with a low FVIII content (Wilfact®)(FVIII : VWF ratio <0.2 : 1).Methods : For this analysis, data for rVWFC comes from post hoc analysis of prospective clinical trial (CT) NCT02973087, 2 and for pd-VWFC (with FVIII), from prospective CT NCT04052698...4Regarding this risk, it could be assumed that VWFCs without FVIII would be exempt from it, but TEs were reported in scheduled surgeries with rVWFC 5 and with other VWFCs/FVIII with a lower proportion of FVIII than the pd-VWFC with FVIII analized (for example, pd-VWFC rich in VWF, Haemate P®)...5,13 With pd-VWFC (ratio VWF/FVIII 1 : 1), the obtained FVIII peak is higher, coinciding with the VWF peak, generating a higher thrombin..."

Clinical • Review • Cardiovascular • Hematological Disorders • Hemophilia • Thrombosis

Platelet Factor 4 (PF4) Binding to Neutrophil Extracellular Traps (NETs) and Von Willebrand Factor (vWF) Improves Bacterial Capture and Killing in an Electrostatic Charge-Dependent Manner (ASH 2024) - "vWF-coated channels were prepared by incubating channels with recombinant vWF (Vonvendi, 50µg/ml) after which they were subjected to flow at 20 dynes/cm2 to promote physiologic factor multimerization...Experiments were repeated with live green fluorescent protein (GFP) expressing E coli strains, including K12 E coli and the colistin-resistant PmrA53 E coli mutant that has reduced negative surface charge. To assess the effect of PF4 on bacterial-retention, NET-lined channels were infused with DNase I (Biolegend) and VWF-channels were infused with recombinant ADAMTS13 (Abcam) and N-acetylcysteine (NAC, Sigma-Aldrich)...PF4 also tethers bacteria to vWF, and while this does not directly promote bacterial killing, it may accelerate bacterial clearance. These results suggest that treatment with PF4 may act synergistically with antibiotics to improve bacterial clearance, with the most pronounced benefit potentially in thrombocytopenic patients."

Hematological Disorders • Infectious Disease • Septic Shock • Thrombocytopenia

Disparities in Real-World Treatment Patterns Among Patients with Von Willebrand Disease in a Large US Population-Based Dataset (ASH 2024) - "On-demand medications included antifibrinolytics and desmopressin, which were used 46% and 31% of the time, respectively, while 23% used VWF replacement therapies. Among prophylaxis users, 49% of patients were treated with VWF replacement therapies, most commonly Humate-P (77%), followed by wilate (16%), Vonvendi (11%), and Alphanate (8%)...Hemlibra was used in 2% of patients, mainly to treat those with joint bleeds...While heavy menstrual bleeding and nosebleeds were the most common bleeding phenotypes among VWD patients with bleeding comorbidities (and likely underrepresented in claims data), only a minority of patients received VWF replacement therapies. These findings suggest a high unmet need for better treatment options for VWD patients who may benefit from prophylactic therapy."

Clinical • HEOR • Real-world • Real-world evidence • Anemia • Gastrointestinal Disorder • Hematological Disorders • Hemophilia

Impact of Tranexamic Acid Administration on Postpartum Hemorrhage in Women with Von Willebrand Disease Receiving Recombinant VWF at Delivery: The VWD Woman Trial (ASH 2024) - P3 | "This investigator-initiated research study received support from Takeda Pharmaceuticals in the form of funding and Vonvendi. Given the 95% observed prevalence of iron deficiency, screening and treatment should be standard in pregnant women with VWD. Better approaches are needed to reduce or prevent the 30% rate of PPH despite treatment."

Clinical • Cardiovascular • Gynecology • Hematological Disorders • Hemophilia • Postpartum Hemorrhage • Thrombosis

Safety, Efficacy, and Pharmacokinetic Evaluation of rVWF in Chinese Subjects With von Willebrand Disease (ChiCTR) - P3 | N=20 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

New P3 trial • Hemophilia

Glioblastoma Multiforme Resection in the Setting of Von Willebrand Disease (ASA 2025) - "He was pretreated with tranexamic acid and Antihemophilic Factor/von Willebrand Factor Complex (Humate-P®) and administered recombinant von Willebrand factor (Vonvendi®) which was continued for two weeks postoperatively. The intraoperative course was uneventful with 500mL blood loss and hemostasis was achieved. Postoperative hematological and coagulation panels were stable, and he was discharged home."

Brain Cancer • Glioblastoma • Hemophilia • Solid Tumor

U.S. FDA Approves Expanded Indication for VONVENDI [von Willebrand factor (Recombinant)] for Adults and Children with Von Willebrand Disease (Businesswire) - "Approval Expands Use of VONVENDI to Include Routine Prophylaxis to Reduce the Frequency of Bleeding Episodes in Adults with Type 1 and 2 Von Willebrand Disease (VWD) and On-Demand and Perioperative Management of Bleeding in Pediatric Patients with VWD....This approval is based on data from three clinical trials...as well as supportive real world data."

FDA approval • Hematological Disorders

A Study of Recombinant Von Willebrand Factor (rVWF) in Chinese Participants With Von Willebrand Disease (vWD) (clinicaltrials.gov) - P3 | N=20 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=31 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Jan 2025 ➔ Mar 2026 | Trial primary completion date: Jan 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Hemophilia

Enhanced α2-3 linked sialylation determines the extended half-life of CHO-rVWF. (PubMed, Blood) - "The half-life of recombinant VWF (rVWF) expressed in CHO cells (CHO-rVWF; Vonicog alfa, VonvendiÒ / VeyvondiÒ) is significantly longer than plasma-derived (pd) VWF concentrates...In contrast to pdVWF, in vivo studies in MGL1-/- mice and Asgr1-/- mice demonstrated that neither MGL nor ASGPR play significant roles in regulating CHO-rVWF clearance. Together, our findings demonstrate that enhanced α2-3 linked sialylation on CHO-rVWF is responsible for its extended in vivo half-life."

Journal • MUC4

A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=38 | Completed | Sponsor: Baxalta now part of Shire | Active, not recruiting ➔ Completed

Trial completion • Hemophilia • Pediatrics

A Study of Recombinant Von Willebrand Factor (rVWF) (TAK-577) in Children With Severe Von Willebrand Disease (vWD) (clinicaltrials.gov) - P3 | N=24 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2027 ➔ Apr 2030 | Trial primary completion date: Feb 2027 ➔ Apr 2030

Enrollment open • Trial completion date • Trial primary completion date • Hemophilia

Prevent Postpartum Hemorrhage in Women with Von Willebrand Disease: the VWD-WOMAN Trial (clinicaltrials.gov) - P3 | N=20 | Completed | Sponsor: Nicoletta C Machin | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Sep 2024

Trial completion • Trial completion date • Hematological Disorders • Hemophilia • Postpartum Hemorrhage

Leveraging National Real-World Evidence to Understand Differences of Economic Burden in Rare Diseases: The Case of Von Willebrand Disease in France (ISPOR-EU 2024) - "Within adult on-demand users, HRUC related to hospitalizations, in-hospital RT and FVIII, outpatient general practitioner and nurse visits, out-hospital RT and FVIII dispensings were assessed by AP and compared across RTs (Wilfactin ® , Veyvondi®, Voncento ® , Eqwilate ® ) using Generalized Estimating Equation models (GEE) accounting for intra-patient correlation and potential confounding factors. This large-scale real-world study is the first comparing costs related to the use of RT available in France. Costs were higher in AP treated with Wilfactin ® or Voncento ® than in those treated with Veyvondi ® ."

Clinical • HEOR • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Rare Diseases

A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=38 | Active, not recruiting | Sponsor: Baxalta now part of Shire | Recruiting ➔ Active, not recruiting | N=71 ➔ 38

Enrollment change • Enrollment closed • Hemophilia • Pediatrics

A rare case of acquired von Willebrand syndrome type 2B: diagnosis, treatment, and underlying pathophysiology. (PubMed, Res Pract Thromb Haemost) - "This AVWS with a 2B phenotype VWD was probably related to a monoclonal immunoglobulin G antibody causing a VWF conformational change, resulting in increased affinity to platelet glycoprotein-Ib. In the event of surgery or bleeding, treatment with vonicog alfa seems to be the best option for this patient."

Journal • Hematological Disorders • Hemophilia • Monoclonal Gammopathy • Thrombocytopenia

Exposure-Response Relationship between VWF/FVIII Activity and Spontaneous Bleeding Events Following Recombinant VWF Prophylaxis in Severe VWD. (PubMed, TH Open) - P3 | "Background  Recombinant von Willebrand factor (rVWF, vonicog alfa, Takeda Pharmaceuticals USA) is indicated in adults diagnosed with von Willebrand disease (VWD)...The model-generated hazard ratio for a 10 IU/dL increment in the average exposure of VWF:RCo 24 hours before a spontaneous BE was 0.651 (95% confidence interval: 0.431-0.982). Conclusions  This ER analysis suggests a causal association between VWF:RCo and spontaneous BEs, with an increase of VWF:RCo exposure leading to a decrease in spontaneous BE risk."

Journal • Hemophilia

Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor in a patient with von Willebrand disease: perioperative optimization for patients with coagulopathies. Illustrative case. (PubMed, J Neurosurg Case Lessons) - "MRgFUS thalamotomy with peri- and postoperative hematological management is a promising alternative to DBS for patients with underlying coagulopathies."

Journal • MRI • Cerebral Hemorrhage • CNS Disorders • Essential Tremor • Hematological Disorders • Hemophilia • Movement Disorders

Localized recombinant human von Willebrand Factor influences in vivo angiogenesis in VWF‐deficient mice (ISTH 2024) - "Matrigel mixed with recombinant fibroblast growth factor (FGF) basic (146 aa), recombinant human vascular endothelial growth factor (VEGF165) and recombinant human VWF (rhVWF, VONVENDI®) at 10 IU/ml was injected subcutaneously in the right back flank of mice (experimental)... Compared to the experimental plugs, controls were dark red, indicating the presence of erythrocytes. These control plugs showed increased capillary formation and red cells on H&E compared to experimental plugs that showed fewer capillaries. A similar pattern was observed on IHC staining as evidenced by higher signals of CD31, which stains murine endothelial cells, in control plugs."

Preclinical • Cardiovascular • Gastrointestinal Disorder • Hemophilia • CD31 • PECAM1

Spectrum of Von Willebrand Disease (vWD) among children at a paediatric hospital in Singapore (ISTH 2024) - "2 of them were eventually started on prophylaxis (1 with Alphanate® and 1 with Vonvendi®). 26 patients with vWD were included in this study. 76.9% were diagnosed with Type I vWD, 19.2% with Type II vWD and 3.9% with Type III vWD. The median age at diagnosis was 5.8 years (range 0-13.6 years) and 34.6% of them had a positive family history of vWD."

Clinical • Hematological Disorders • Hemophilia • Pediatrics

ECMO Platelet Dysfunction and the Quandary of Evaluating Treatment with rvWFC in a Prospective Ex-vivo Approach: A Testability Predicament (ISTH 2024) - "Primary hemostasis and platelet function were evaluated using PFA-100 (Siemens Healthineers) and Multiplate-Analyzer (Roche Diagnostics) measurements of blood samples either untreated or spiked with recombinant vWFC (rvWFC, Vonicog alfa, Takeda Pharmaceutical), equivalent to 80 IU/kg body weight... In healthy donors, rvWFC significantly improved platelet function, as measured by Multiplate RISTO-test (p=0.0499), although not seen in TRAP-test (p=0.7794) or COL-test (p=0.0929). PFA-100 measurements showed a trend of improvement in the COL/EPI-assay (p=0.0679) and COL/ADP-assay (p=0.0679). Compared to healthy, platelet dysfunction was present in ECMO-patients, but no improvement in function by rvWFC was observed in any of the tests (p>0.05), probably due to unmet preconditions for reliable results."

Preclinical • Hematological Disorders

A Study on the Outcomes of Recombinant Von Willebrand Factor on Demand Treatment and Prevention and Treatment of Bleeding During and After Surgery in Adults With Inherited Von Willebrand Disease in the United Kingdom (UK) (clinicaltrials.gov) - P=N/A | N=34 | Completed | Sponsor: Takeda

New trial • Surgery • Hemophilia

Healthcare resource utilisation of patients with VWD treated with recombinant Von Willebrand factor: Chart review (BSH 2024) - "Background: There is a paucity of real-world evidence (RWE) that describes healthcare resource utilisation (HRU) of patients with von Willebrand disease (VWD) who are treated with recombinant von Willebrand factor (rVWF; vonicog alfa)... The results presented here are, to our knowledge, the first to report RWE of HRU in UK patients with VWD treated OD to treat spontaneous/traumatic bleeds or to prevent/treat surgical bleeds. More research is required to assess HRU in patients with VWD across treatment centres both within and outside of the UK."

Clinical • HEOR • Review • Critical care • Hematological Disorders • Hemophilia