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Congenital and acquired disorders of coagulation
Published in Jennifer Duguid, Lawrence Tim Goodnough, Michael J. Desmond, Transfusion Medicine in Practice, 2020
Jeanne M Lusher, Roshni Kulkarni
Genetics Institute’s B-domain-deleted (BDD) rFVIII, ReFacto, is a truncated FVIII molecule that lacks the middle section (B domain). This much smaller molecule is secreted more efficiently by CHO cells. The currently licensed version (licensed by the US FDA in 2000, and earlier in Europe) contains no added HSA, but HSA is used in the culture medium. A newer version of ReFacto (currently in pre-licensure clinical trials), contains no albumin. Similarly, as of April 2002, Recombinate, which is completely albumin-free, is in pre-licensure clinicals trials in persons with haemophilia A.
Budget impact of prophylactic treatment of rVIII-SingleChain in moderate and severe hemophilia A in Italy
Published in Journal of Medical Economics, 2023
Eugenio Di Brino, Songkai Yan, Radovan Tomic, Marco Panebianco, Ewa Dlotko, Lee Stern, Michele Basile, Filippo Rumi, Americo Cicchetti, Renato Marino
A budget impact analysis was developed to estimate the annual budget impact of the increasing usage of rVIII-SingleChain for prophylactic treatment of moderate and severe hemophilia A patients over 3 years from the Italian National Health Service (NHS) perspective. In addition to rVIII-SingleChain, the currently available products in the Italian setting are rFVIIIFc (ELOCTA, Sobi), BAX 855 (ADYNOVATE/ADYNOVI, Takeda), BAY 94-9027 (JIVI, Bayer), N8-GP (ESPEROCT, NovoNordisk), BAY 81-8973 (KOVALTRY, Bayer), Human cl-rhFVIII (NUWIQ, Octapharma), octocog alfa (ADVATE, Takeda), BDD-rFVIII (REFACTO AF, Pfizer), N8 (NOVOEIGHT, NovoNordisk), or a non-factor replacement product (emicizumab, HEMLIBRA, Roche). The model was developed to account for two distinct patient populations: patients receiving prophylaxis (including regular prophylactic treatment and the treatment of breakthrough bleeds occurring while receiving a prophylactic regimen) and patients without prophylaxis receiving episodic (on demand) treatment of bleeds (hereafter referred to as “episodic treatment”); since the consumption of factor replacement products is lower in episodic treatment compared to prophylaxis in the Italian setting, the current analysis focuses on prophylactic treatment only. See the Appendix for additional methods and results considering episodic treatment.
Safety of recombinant coagulation factors in treating hemophilia
Published in Expert Opinion on Drug Safety, 2019
Massimo Morfini, Carlo Antonio Paolo Rapisarda
After the introduction of recombinant FVIII concentrates, several observational studies, mostly retrospective, provided different figures about the incidence of anti-FVIII inhibitors, ranging from 24% [21] to 33% [22] in patients treated for the first time with pd- or rFVIII, up to a maximum of 52% in patients affected by severe hemophilia A [23]. In Italy, in a medium-sized cohort study (n = 64) of patients treated from 1975 to 1982 with pdFVIII, a relatively low incidence of anti-FVIII inhibitors was observed (20.3%) after the first 20 Eds, which increased to 27% after 700 Eds [24]. Prospective observational studies conducted in PUPs, mandatory in phase I/II studies for the registration of the new recombinant concentrates, provided much more reliable and homogeneous data. In fact, according to these regulatory studies, the incidence of anti-FVIII inhibitors was equal to 29.7% for Kogenate (Bayer), 31% for Recombinate (Baxter) and 33% for Refacto (Pfizer) [25]. In a previous study conducted in 93 hemophilia A patients in the USA, the incidence of inhibitors was 38% after the first 18 Eds to Kogenate [26]. The implementation in hemophilia therapy of the first B-domain deleted (BDD) concentrate, Refacto (Pfizer), raised some concerns about the efficacy and immunogenicity of this modified molecule [27–32] not confirmed afterward by other treaters [33–36]. Most of the new rFVIII EHL are BDD or B domain truncated: being the B domain highly glycosylated, the removal of B domain improves the secretion and the yield of this modified FVIII molecule in the medium of cell cultures [37].
Current and Future Options of Haemophilia A Treatments
Published in Expert Opinion on Biological Therapy, 2021
Wolfgang Miesbach, Fagr Eladly
Recently, four EHL FVIII products have been approved for the prophylactic and needs-based treatment of hemophilia A. Like the standard products such as the plasma-derived FVIII concentrates or the recombinant products, Octocog alfa (Advate®), Lonoctocog alfa (Afstyla®), Simoctocog alfa (Nuwiq®), Octocog alfa (Kovaltry®), Turoctocog alfa (NovoEight®), Moroctocog alfa (ReFacto AF®), the EHL products belong to the third generation of recombinant FVIII and do not contain animal or human plasma proteins as end products.