Fanhdi (human plasma derived coagulation factor VIII) / Grifols - LARVOL DELTA

Safety and Efficacy of the Use of pdVWF/FVIII-C in Patients with von Willebrand Disease: A Prospective, Observational, Post-Authorization Study. (PubMed, Clin Appl Thromb Hemost) - "No clinical signs and symptoms of immunogenicity or thromboembolic events were reported.ConclusionsThis real-world evidence study confirmed the efficacy of the pdVWF/FVIII-C as on-demand and/or prophylaxis treatment in patients with bleeding episodes or surgical procedures in VWD. Fanhdi® was well tolerated without any safety concerns."

Journal • Observational data • Cardiovascular • Gastrointestinal Disorder • Hemophilia

Cost-effectiveness and cost-utility analysis of haemate-P versus other von willebrand disease treatments in Spain. (PubMed, J Med Econ) - "Treatment strategies compared included Haemate-P, Fanhdi, and Wilate in long-term prophylaxis (LTP) or on-demand treatment (ODT). Results were generally robust to sensitivity analyses. In patients with severe vWD experiencing a high bleed rate, Haemate-P prophylaxis is a less costly and potentially more effective treatment strategy and Haemate-P is cost-saving among on-demand strategies."

HEOR • Journal • Hematological Disorders • Hemophilia

Ex vivo evaluation of the effect of plasma-derived factor VIII/von Willebrand factor in patients with severe hemophilia A on emicizumab prophylaxis. (PubMed, Clin Exp Med) - "Samples from healthy controls (HC) and HA patients were drawn in sodium citrate plus corn trypsin inhibitor tubes and spiked with increasing concentrations of pdFVIII/VWF concentrates (10-400 IU/dL) (Fanhdi®/Alphanate®, Grifols), activated prothrombin complex concentrate (aPCC, 0.5 U/mL) or recombinant activated factor VII (rFVIIa, 0.9 µg/mL). Coagulation parameters of both methods significantly correlated at baseline and with increasing concentrations of pdFVIII/VWF. High doses of pdFVIII/VWF concentrates, similar to those used for ITI, did not trigger a multiplying procoagulant effect to samples from HA patients on emicizumab prophylaxis, evidencing their low thrombotic risk in these patients."

Journal • Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Monitoring the Hemostatic Effects of Inhibitory Alloantibodies in Von Willebrand Disease Using Global Coagulation Assays (ASH 2024) - "We evaluated the efficacy of various global coagulation tests and thrombus formation assays to monitor the effect of anti-VWF inhibitors on the response to plasma-derived (pd) VWF/FVIII treatment in a case of VWD that developed alloantibodies.MethodsA 23-year-old man with type3 VWD, who started on prophylaxis with pdVWF/FVIII concentrates (Fanhdi®) at the age of 3 years, has been followed up since 2021...However, the total recovery of T-TAS AUC values is only obtained using blood samples without inhibitor (0 BU) (AR_AUC wo : 1100 vs w : 201-878; PL_AUC wo : 273 vs w : 53-164), and a high inverse correlation (r : -0.95; p<0.05) was observed between sample inhibitor levels and AUC values obtained after addition of increasing doses of pdVWF/FVIII.ConclusionThe flow chamber-based T-TAS system proved to be a reliable point-of-care device for monitoring the effect of alloantibodies on the hemostatic response to replacement therapies in VWD. Further studies are needed..."

Clinical • Hematological Disorders • Hemophilia • Thrombosis

Real-World Efficacy and Safety of Plasma-Derived Von Willebrand Factor-Containing Factor VIII Concentrates in Patients With Von Willebrand Disease in Italy. (PubMed, Clin Appl Thromb Hemost) - "As far as safety, no adverse-drug-related episodes, immunogenic or thrombotic events were reported. This study confirmed that Fanhdi® and Alphanate® were effective and safe in the management of bleeding episodes, the prevention of bleeding during surgeries and for SLTP in Italian patients with inherited VWD."

Journal • Real-world • Real-world effectiveness • Real-world evidence • Hemophilia

Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease (clinicaltrials.gov) - P4 | N=8 | Recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Apr 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Hemophilia • Pediatrics

Safety and efficacy of the use of Fanhdi® in patients with von Willebrand disease: a prospective, observational, post-authorization study (WFH 2024) - No abstract available

Clinical • Observational data • Hemophilia

Monitoring of Hemostatic Status and Treatment Response in Von Willebrand Disease Using a Microchip Flow Chamber Assay (ASH 2023) - "The effect of ex vivo administration of 100, 150 and 300 IU/dL of pdVWF/FVIII (Fanhdi ®, Grifols) was also evaluated. Monitoring treatment efficacy in VWD using a flow chamber-based thrombus formation analysis system could be a reliable and standardized method to assess the response to desmopressin and pdVWF/FVIII concentrates in patients with VWD, allowing an optimal personalized therapeutic dosing and a better prevention of bleeding episodes in these patients."

Hemophilia • Thrombosis

Cost-Utility Analysis for Haemate-P in the Treatment of Von Willebrand Disease (ISPOR-EU 2023) - " Under all treatment strategies, Haemate-P presents better ICER results than its alternative products (Fanhdi and Wilate). Haemate-P presents better ICER results alternative under all treatment strategies, especially when used as a long-term prophylaxis treatment."

HEOR • Hematological Disorders • Hemophilia

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

REAL-WORLD EFFICACY AND SAFETY OF PLASMA-DERIVED VON WILLEBRAND FACTOR-CONTAINING FACTOR VIII CONCENTRATES IN PATIENTS WITH VON WILLEBRAND DISEASE IN ITALY (EAHAD 2023) - "This real-world evidence study confirmed that pdVWF/FVIII concentrates, Fanhdi and Alphanate, were effective and safe in the management of bleeding episodes and in the prevention of bleeding during surgeries in Italian patients with VWD."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Hemophilia

EVALUATION OF TREATMENT RESPONSE IN VON WILLEBRAND DISEASE USING A FLOW-BASED THROMBUS FORMATION ASSAY (EAHAD 2023) - "Treatment of type-3 patients with Fanhdi® or Wilate (40U/Kg) normalized levels of VWF:RCo (76% after treatment) but slightly increased OT/AUC thrombus formation parameters. Personalized analysis of the treatment effect in VWD using a microchip flow-chamber system (T-TAS®) could be a reliable methodology to monitoring the DDVAP response and the optimal individualized dosage of pdVWF/FVIII concentrates for each VWD patients allowing a better prevention of bleedings or thrombotic events. Funding: Grifols and Zacros"

Hemophilia • Thrombosis

Ex vivo study of the concomitant use of plasma-derived Factor VIII/Von Willebrand Factor and emicizumab in patients with severe Hemophilia A (ISTH 2022) - "Aims: To evaluate the procoagulant effect of ex vivo combination of samples from HA patients treated with emicizumab with a pdFVIII/VWF concentrate (Fanhdi®, Grifols). Emicizumab treatment alone did not restore clotting to normal levels. The addition of pdFVIII/VWF at 50 IU/dL (≡25 IU/kg) restored these parameters within HCs normal range, similar to that observed after the addition of rFVIIa. Even higher doses of pdFVIII/VWF, up to 200IU/kg, did not result in excessive procoagulant profile."

Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

Evaluation of thrombin generation capacity of plasma-derived Factor VIII/von Willebrand Factor in the Treatment of von Willebrand Disease (ISTH 2022) - "TP levels increased dose-dependently with increasing FVIII concentrations and were similar between Fanhdi® and Humate-P® (Figure 1). VWD plasmas with endogenous FVIII (VWD1, VWD2A and VWD2B) needed lower doses of pdFVIII/VWF concentrate to reach normal TP range, while in FVIII-deficient samples (VWD3), TP was restored within the normal range at a higher dose (200 IU/dL). The highest TP was observed with endogenous FVIII (VWD1) samples spiked with Fanhdi® (584.6 [55] nM) and Humate® (586 [79.7] nM) at the highest FVIII dose, although TP levels were within normal range."

Hemophilia

Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease (clinicaltrials.gov) - P4 | N=8 | Recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Dec 2022 ➔ Dec 2024 | Trial primary completion date: Apr 2022 ➔ Apr 2024

Trial completion date • Trial primary completion date • Hemophilia • Pediatrics

PERIOPERATIVE MANAGEMENT IN “NON-SEVERE” HEMOPHILIA PATIENTS (EAHAD 2022) - "Tranexamic acid was administered as unique hemostatic therapy in 6 procedures and DDAVP in 7 surgeries...1 HA patient received combined therapy with rFVIII and von Willebrand factor (Fanhdi®) in 2 surgeries... Hemostatic management during a surgical procedure hospitalization in Hemophilia patients requires a multidisciplinary approach. Perioperative hemostatic protocols optimize the management and minimize the challenge of bleeding complication during invasive procedures in patients diagnosed of congenital coagulopathies."

Clinical • Critical care • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Rare Diseases

EFFECT OF PLASMA-DERIVED FACTOR VIII/VON WILLEBRAND FACTOR IN PATIENTS WITH SEVERE HEMOPHILIA A ON PROPHYLAXIS WITH EMICIZUMAB: AN EX VIVO EVALUATION WITH A THROMBIN GENERATION ASSAY (EAHAD 2022) - "In this study we evaluated thrombin generation (TG) resulting from ex vivo combination of plasma samples from hemophilia A (HA) patients treated with emicizumab, with a plasma-derived Factor VIII/Von Willebrand Factor (pdFVIII/VWF) concentrate (Fanhdi®, Grifols). Concomitant use of pdFVIII/VWF in HA patients with prophylaxis with emicizumab did not trigger a multiplying effect on TG. These results suggest a low risk of overdose and thrombotic events of concomitant treatment emicizumab with the pdFVIII/VWF concentrate in HA patients."

Preclinical • Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases

Clinical Efficacy and Safety of Fanhdi, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study. (PubMed, Clin Appl Thromb Hemost) - "Fanhdi was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients."

Journal • Retrospective data • Hemophilia

[VIRTUAL] DRAWBACKS OF PERSONALIZATION OF PROPHYLAXIS AMONG ADULT MEN WITH HEMOPHILIA A (HEMO 2021) - "Five men with HA (2 receiving Beriate®, 1 moderate and 1 severe; and 3 receiving Fanhdi®, 2 moderate and 1 severe) were included. We believe personalization of therapy is important to guarantee joint health and quality of life of PwHA. However, based on the analyses of the individual cases we reported, adherence to treatment may be an important impacting factor to consider among adult PwHA."

Clinical • Hematological Disorders • Hemophilia • Human Immunodeficiency Virus • Infectious Disease • Rare Diseases • Rheumatology

Ex Vivo Evaluation of the Effect of Plasma-Derived Factor VIII/Von Willebrand Factor in Patients with Severe Hemophilia_A on Prophylaxis with Emicizumab By Thrombin Generation Assay (ASH 2021) - "The aim of this study was to evaluate the TG resulting from ex vivo combination of plasma samples from HA patients treated with emicizumab, with a pdFVIII/VWF concentrate (Fanhdi ® , Grifols). The concomitant use of pdFVIII/VWF in patients with prophylaxis with emicizumab did not trigger a multiplying effect on TG. These results were aligned with previous in vitro data and suggested the low risk of overdose and thrombotic events of concomitant treatment emicizumab with the pdFVIII/VWF concentrate in HA patients."

Preclinical • Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases

Efficacy and safety evaluation of Fanhdi , a plasma-derived factor VIII/ von Willebrand factor concentrate, in Von Willebrand's disease patients undergoing surgery or invasive procedures: A prospective clinical study. (PubMed, Haemophilia) - No abstract available

Clinical • Journal

CLINICAL EFFICACY AND SAFETY OF PLASMA-DERIVED VON WILLEBRAND FACTOR- FVIII COMPLEX CONCENTRATES, IN PATIENTS WITH VON WILLEBRAND DISEASE IN ITALY: STUDY DESIGN. (BIC 2021) - "Materials and This is a multicentric study of patients diagnosed with congenital VWD and treated with Fanhdi® or Alphanate® for the management of bleeding and surgery and for secondary long-term prophylaxis, when desmopressin is ineffective or contraindicated. In Italy, the efficacy and safety of the study concentrates has been already proven in patients with VWD. However, this retrospective study will provide further evidence supporting the use of highly purified pdFVIII/VWF concentrates Fanhdi® and Alphanate®, for treating VWD in routine clinical practice."

Clinical • Hemophilia

Clinical benefits of a Bayesian model for plasma-derived factor VIII/VWF after one year of pharmacokinetic-guided prophylaxis in severe/moderate hemophilia A patients. (PubMed, Thromb Res) - "PK-guided prophylaxis with a specific pdFVIII/VWF popPK model allowed treatment individualization and improved bleeding control in routine clinical practice, especially in younger patients with short pdFVIII/VWF half-lives."

Clinical • Journal • PK/PD data • Hematological Disorders • Hemophilia • Osteoarthritis • Rare Diseases

[VIRTUAL] VWF‐CONTAINING FVIII CONCENTRATES IMPROVE FVIII RECOVERY IN A MOUSE MODEL OF SEVERE HAEMOPHILIA WITH INHIBITORS (EAHAD 2021) - "FVIIInull E16 Knockout (KO) mice (n = 4-12), previously infused with either vehicle or inhibitor (to achieve high titer ̴ 6 BU/mL), were treated with FVIII concentrates at therapeutic doses (100 IU/kg) from different sources: native pdFVIII/VWF complex (Fanhdi®), full length rFVIII from Baby Hamster Kidney cells (Kovaltry®), single-chain (SC) B-domain-deleted (BDD) rFVIII from Chinese Hamster Ovary cells (Afstyla®), BDD-rFVIII from Human Embryonic Kidney (HEK) cells (Nuwiq®) and extended half-life BDD-rFVIII-Fc fusion from HEK cells (Elocta®)... In agreement to previously reported data, native pdFVIII/VWF concentrate was more efficient in the restoration of FVIII circulating levels in FVIIInull E16 KO mice even in the presence of high inhibitor titer. This finding is similar for the different isolated FVIII concentrates analyzed, regardless their origin, molecular form, cell line or involved modifications."

Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease (clinicaltrials.gov) - P4; N=8; Recruiting; Sponsor: Grifols Therapeutics LLC; Trial completion date: Apr 2020 ➔ Dec 2022; Trial primary completion date: Apr 2020 ➔ Apr 2022

Clinical • Trial completion date • Trial primary completion date • Hemophilia • Pediatrics