Willfact (human von Willebrand factor) / LFB SA - LARVOL DELTA

Prospective Observation on the Use of Von Willebrand Factor (VWF) Concentrates in a Large Cohort of Type 3 Von Willebrand Disease (VWD): Interim (18-months) Analyses on 149 Cases Enrolled into the 3Winters-Ips Project (ASH 2018) - P=N/A; "Being 3WINTERS-IPS a non-interventional study, the therapeutic approaches such as on demand (OD) or secondary long-term prophylaxis (SLTP) with the assigned VWF concentrates with or without FVIII (FANHDI, HAEMATE-P, WILATE, WILFACTIN) were decided by local investigators. So far, the use of SLTP seems to reduce the ABR. However, a longer prospective observation (from 2 to 5 years) with 3WINTERS-IPS-EXTENDED is required to characterize bleeding phenotype of VWD3 patients and to prepare recommendations on the appropriate use (OD/SLTP) of the VWF concentrates"

Clinical • Biosimilar

TREATMENT WITH A PLASMA-DERIVED VON WILLEBRAND FACTOR (VWF) ALMOST DEVOID OF FACTOR VIII IN PAEDIATRIC PATIENTS WITH VON WILLEBRAND DISEASE (VWD): A POOLED ANALYSIS (EAHAD 2023) - "Introduction: VWF replacement therapy is the mainstay of treatment for VWD patients when desmopressin is ineffective or contraindicated... The data shows that a plasma derived VWF concentrate with low FVIII content (WILFACTIN®/WILLFACT®) is efficacious and has a favourable safety profile in VWD paediatric patients. As with adults, the dose and duration of treatment should be adjusted to the clinical conditions of the patient and to the VWF:RCo and FVIII:C plasma levels during treatment."

Retrospective data • Gastrointestinal Disorder • Hemophilia • Musculoskeletal Diseases • Orthopedics • Pediatrics • Urology

Structure and Function of Recombinant versus Plasma-Derived von Willebrand Factor and Impact on Multimer Pharmacokinetics in von Willebrand Disease. (PubMed, J Blood Med) - "Recombinant von Willebrand factor (rVWF, vonicog alfa) is a purified VWF concentrate produced from Chinese hamster ovary cells...rVWF also demonstrated higher FVIII binding capacity than Haemate P, Voncento and Wilate. Modeling provided evidence that VWF:RCo activity in patients with severe VWD treated with rVWF is associated with L/UL VWF multimers in the circulation. Findings suggest that the L and UL multimers preserved in rVWF contribute to high biological activity and might be important for providing hemostatic efficacy."

Journal • PK/PD data • Hemophilia

TREATMENT WITH A PLASMA-DERIVED VON WILLEBRAND FACTOR (VWF) ALMOST DEVOID OF FACTOR VIII IN ELDERLY PATIENTS WITH VON WILLEBRAND DISEASE (VWD): A POOLED ANALYSIS (EAHAD 2022) - "This analysis revealed that a VWF with low FVIII content is safe in elderly patients with VWD in all clinical situations including surgery, with efficacy and dosing data comparable to those of adults."

Retrospective data • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Hemophilia • Musculoskeletal Diseases • Oncology • Orthopedics • Urology

[VIRTUAL] Effects of von Willebrand Factor on Plasma Haemostasis (ISTH 2021) - "Conclusions : Taken these effects together it suggests that plasma coagulation in VWF deficiency results in relatively more rapid coagulation due to larger effects of factor VIII, more clot stabilization in TM-rich environment, and a lower rigidity. These opposite effects may modulate the bleeding profile."

Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] MANAGEMENT OF PATIENTS WITH VON WILLEBRAND DISEASE UNDERGOING PROPHYLAXIS FOR GASTROINTESTINAL BLEEDING: RESULTS OF A POST‐MARKETING STUDY WITH A HIGH‐PURITY PLASMA‐DERIVED VON WILLEBRAND FACTOR (EAHAD 2021) - "In this study, routine prophylaxis with a high-purity pdVWF was well tolerated and contributed to an effective management of recurrent GI bleeding."

Clinical • P4 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hemophilia

[VIRTUAL] MANAGEMENT OF PATIENTS WITH VON WILLEBRAND DISEASE UNDERGOING PROPHYLAXIS FOR JOINT BLEEDING: RESULTS OF A POST‐MARKETING STUDY WITH A HIGH‐PURITY PLASMA‐DERIVED VON WILLEBRAND FACTOR. (EAHAD 2021) - "In this study, the pdVWF almost devoid of FVIII was effective and well tolerated in joint BE prophylaxis. Benefits reported in this real-world patient study confirm the results of a phase III study assessing specifically the long-term prophylaxis with this pdVWF."

Clinical • P4 data • Hematological Disorders • Hemophilia • Rare Diseases • Rheumatology

[VIRTUAL] Safety and efficacy of a high-purity plasma derived von Willebrand Factor in patients with von Willebrand disease (VWD) undergoing prophylaxis for joint bleeding: results from a post-marketing study (GTH 2021) - "The objective was to evaluate the safety and efficacy of a prophylactic treatment with a plasma derived Factor VIII-poor von Willebrand Factor (pdVWF) concentrate (Wilfactin®/ Willfact® - LFB) in routine clinical use...Conclusion In this study, the FVIII-poor pdVWF has been effective and well tolerated in joint bleeding prophylaxis. Benefits reported in this real-world patient study confirm results of a phase III study assessing specifically the long-term prophylaxis with this pdVWF."

Clinical • P4 data • Hematological Disorders • Hemophilia • Rare Diseases • Rheumatology

[VIRTUAL] Safety and efficacy of a high-purity plasma-derived von Willebrand Factor in patients with von Willebrand disease (VWD) undergoing prophylaxis for gastrointestinal bleeding: results from a post-marketing study (GTH 2021) - "The objective was to evaluate the safety and efficacy of a plasmatic Factor VIII-poor von Willebrand Factor (pdVWF) concentrate (Wilfactin®/ Willfact® - LFB) in routine clinical use...During a prolonged exposure, the pdVWF was well tolerated without report of thrombotic events, neutralising VWF inhibitors or any other related serious adverse events. Conclusion In this study, routine prophylaxis with pdVWF was well tolerated and contributed to an effective management of recurrent GI bleeding."

Clinical • P4 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hemophilia

[VIRTUAL] Recombinant Human von Willebrand Factor (rVWF) Differs in Structure and Function from Plasma Derived Concentrates (ISTH 2020) - "Aims: Structural and functional comparison of clinically used pd and rVWF concentrates: pdFVIII/VWF: HAEMATE P/HUMATE-P, VONCENTO (CSL Behring, King of Prussia, USA); WILATE/EQWILATE (Octapharma, Lachen, Switzerland)pdVWF: WILFACTIN/WILLFACT (LFB, Courtaboeuf, France)rVWF: VONVENDI/VEYVONDI Cross-product comparisons included VWF content by determination of VWF: Ag, and biological function assessed by VWF: RCo, VWF: CB, and VWF: GpIbM (VWF activity assay Innovance; Siemens) using routine commercial test kits. VWF products differ in their contents, multimer size and structure of functional VWF. These differences may translate into improved biological activity of rVWF in clinical settings and influence the treatment regimen of individuals with VWD."

Targeted Protein Degradation

[VIRTUAL] The Homozygous Variant p.Gln1311* in Exon 28 of VWF Is Causing Type 3 von Willebrand Disease and Is at High Risk of Allo-Immunisation (ISTH 2020) - "A prophylaxis treatment has been initiated with plasma-derived VWF and FVIII (Wilfactin® ± Factane®) for all patients after their diagnosis of type 3 VWD because of severe bleeding symptoms (ISTH-BAT score: 14-24)... We identified the p.Gln1311* variant as a type 3 VWD variant associated with a high risk of allo-immunisation. This information must be considered for future patients in the discussion of prophylaxis instauration."

Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Management of von Willebrand disease with a factor VIII-poor von Willebrand factor concentrate: results from a prospective observational post-marketing study. (PubMed, J Thromb Haemost) - "Results from this PMS increase the clinical experience of a FVIII-poor pdVWF in patients of all ages and VWD types including those with thrombotic risk factors and emphasize that giving FVIII is not always mandatory to effectively treat patients with severe VWD."

Clinical • Journal • Observational data • P4 data

PHAM: Prevention of Hemorrhage After Implantation of Mechanical Circulatory Support (clinicaltrials.gov) - P3; N=31; Terminated; Sponsor: University Hospital, Lille; N=156 ➔ 31; Trial completion date: Jan 2020 ➔ Sep 2018; Recruiting ➔ Terminated; Trial primary completion date: Jan 2020 ➔ Sep 2018; deficient inclusion

Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Infusion Requirements in On Demand Treatment of Bleeding Events in von Willebrand Disease (VWD): an Indirect Treatment Comparison between Recombinant von Willebrand Factor (VWF) and Plasma Derived VWF Concentrates (ISTH 2019) - "...Aims: Here we present data from indirect treatment comparisons between recombinant VWF (rVWF, vonicog alfa) and 3 commonly used pdVWF concentrates, using patient-level data from the phase 3 on demand clinical study with rVWF (Gill JC et al...Haemophilia 2003 (Humate P), Borel-Derlon A et al. J Thromb Haemost 2007 (Wilfactin), and Berntorp E et al. Haemophilia 2009 (Wilate)... Overall, the indirect treatment comparisons indicate fewer infusions of rVWF compared to pdVWF may be needed to control a bleed. Several assumptions and limitations of the analysis are noted; e.g., assessments and treatment decisions in different studies were assumed to be comparable. Despite these limitations, the data generated suggest the potential value of VWD bleed treatment with rVWF."

The Management of Patients with von Willebrand Disease (VWD) Undergoing Surgery by Using a Pure Plasma Derived VWF is Easy, Efficient and Safe (ISTH 2019) - "...between Jan 1 rst 2016 and Dec 31 rd 2018 treated with a pure (without FVIII) pdVWF concentrate (Wilfactin® from LFB), the only one VWF concentrate used in our center... Based on our experience, the management of patients with any type of VWD in surgery by using a pure VWF concentrate is simple, efficient and safe. Few pts need a co administration of FVIII at 1 rst VWF injection."

Clinical

Effects of pharmacokinetic models in dosing of DDAVP and/or von Willebrand factor-containing concentrates in patients with von Willebrand disease Effecten van farmacokinetische modellen bij het doseren van DDAVP en/of von Willebrand factor-bevattende concentraten in patiënten met von Willebrandziekte (clinicaltrialsregister.eu) - P4; N=120; Sponsor: Erasmus University Medical Center

Clinical • New P4 trial