Delving into the Latest Updates on Recombinant factor VIII(rEVO Biologics, Inc.) with Synapse

Overview

Basic Info

Drug Type

Recombinant coagulation factor

Synonyms

Factane

Target

F10

Mechanism

F10 stimulants(Coagulation factor X stimulants), Blood coagulation pathway activation, Coagulation factor VIII replacements

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication-

Inactive Indication

Hemophilia A

Originator Organization

rEVO Biologics, Inc.

Active Organization-

Inactive Organization

rEVO Biologics, Inc.

Drug Highest PhasePendingPhase 3

First Approval Date-

Regulation-

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Abstract Background A plasma-derived factor VIII product (pdFVIII; Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF; Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in hemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels. Aim To evaluate the perioperative hemostatic efficacy and safety of these concentrates administered by CI. Methods Three phase III trials were conducted. Adults with HA (FVIII:C < 1%) (studies 1 and 2) or VWD (VWF:RCo < 20%) (Study 3) received a preoperative bolus followed by CI of undiluted concentrate for at least 6 days. Bolus doses and CI rates were based on individual recovery and clearance, respectively. The initial infusion rate had to be higher for 48 hours for HA and 24 hours for VWD patients to anticipate potential fluctuations of factor concentrations during major surgery. Target levels of FVIII:C in HA and VWF:RCo in VWD were 80 and 70 IU/dL, respectively. Efficacy was assessed using a global hemostatic efficacy score. Results Studies 1, 2, and 3 included 12, 4, and 6 patients, respectively. Efficacy outcomes were excellent/good in all 22 major surgeries including 18 orthopedic procedures. Most daily measured FVIII and VWF levels (92%) were on target. No safety concerns, thrombotic events, or inhibitors were identified. Conclusion pdFVIII and pdVWF administered by CI represent an effective and safe alternative to bolus injections in patients with severe HA or VWD undergoing surgery.

01 Jan 2018·HaematologicaQ1 · MEDICINE

Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A

Q1 · MEDICINE

Article

Author: Goudemand, Jenny ; d'Oiron, Roseline ; Vinciguerra, Christine ; Chambost, Hervé ; Dalibard, Vincent ; Huguenin, Yoann ; Rothschild, Chantal ; Lutz, Patrice ; Gruel, Yves ; Calvez, Thierry ; Doncarli, Alexandra ; Demiguel, Virginie

Around one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more life-threatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibitors in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated cohort of patients was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII <1 IU/dL) first treated with one of the three factor VIII products studied. Details of product infusions, inhibitor assays and main fixed and time-varying inhibitor risk factors were recorded for the first 75 exposure days. Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated inhibitors) were analyzed by univariate and multivariate Cox models. We studied 395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane, Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors was significantly associated with the factor VIII product received (P=0.005): the cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7-20.6) with Factane, 20.4% (95% CI: 14.0-29.1) with Advate, and 31.6% (95% CI: 23.5-41.7) with Kogenate Bayer. The low inhibitor incidence observed with Factane is concordant with recent findings from the SIPPET randomized trial. These consistent results from observational and experimental studies should lead to improved care for previously untreated patients and cost savings for healthcare systems worldwide.

01 Jul 2012·Vox SanguinisQ4 · MEDICINE

A qualitative and quantitative analysis of von Willebrand factor contained in a very high‐purity plasma‐derived FVIII concentrate

Q4 · MEDICINE

Article

Author: C. Michalski ; M.-H. Andre ; M.-P. Brandin ; Z. Tellier ; B. Samor ; S. Chtourou

Background and Objectives We studied the structural and functional properties of von Willebrand factor (VWF) molecules present in a very high‐purity plasma‐derived factor VIII concentrate (VHP pdFVIII – Factane®) because several observations suggest that the presence of VWF in factor VIII (FVIII) preparations may decrease their immunogenicity.Materials and Methods Ten marketed batches of VHP pdFVIII (Factane®) with levels of VWF ranging from 15 to 39 IU/100 IU FVIII were analysed. The VWF multimeric pattern was studied by agarose gel electrophoresis. The binding of VWF to FVIII was studied by gel filtration and ELISA. The binding of VWF to GPIb was analysed by ELISA.Results The results showed that high‐molecular‐weight multimers of VWF were present in VHP pdFVIII (Factane®). VWF subunits maintain a triplet structure similar to that of normal plasma. Regardless of the VWF content, all FVIII molecules of each batch were co‐eluted with VWF, and no free FVIII was detectable. By immunoassays, VWF was found to be able to bind to FVIII and platelet GPIb in a similar manner to that of VWF in normal plasma.Conclusions In all the VHP pdFVIII (Factane®) batches studied, regardless of the level of VWF, the structure and capacity of VWF binding to FVIII and to platelet GPIb were fully preserved.

100 Deals associated with Recombinant factor VIII(rEVO Biologics, Inc.)

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