Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?

Abstract

Hemophilia A (HA) is a common bleeding disorder caused by the deficiency of factor VIII (FVIII) with an incidence of ~1 in 5000 male births. Replacement of FVIII is necessary to prevent and treat bleeding episodes. However, with multiple new drugs in addition to old standards, choosing among the different FVIII treatment options is harder than ever. There are FVIII products that are plasma derived or recombinant, FVIII products designed to extend the half-life of FVIII, and the first single-chain FVIII product, recombinant factor VIII single chain (rFVIII-SC). As development of inhibitors to FVIII continues to be a major problem in the care of HA patients, recent studies showing lower rates of inhibitor development with plasma-derived FVIIII products versus recombinant FVIII products have made choosing among the many options now available even more complex. Although still unproven, extended half-life (EHL) products may provide the hope of decreased immunogenicity but need further testing in previously untreated patients (PUPs). This review highlights some of the differences between FVIII products currently available and hopefully assists the clinician to decide which FVIII product to choose for their patients.

Estimation of Nuwiq®(simoctocog alfa) activity using one‐stage and chromogenic assays—Results from an international comparative field study

“…Nuwiq ® (simoctocog alfa, human‐cl rhFVIII; Octapharma) is a fourth‐generation BDD rFVIII produced in a human cell line with human‐like post‐translational protein processing and without chemical modification or fusion to any other protein . Nuwiq ® is effective in the prevention and treatment of bleeds and for bleeding management during surgery in adults and children with haemophilia A and has demonstrated low immunogenicity in previously untreated patients …”

Long‐term tolerability, immunogenicity and efficacy of Nuwiq® (human‐cl rhFVIII) in children with severe haemophilia A

“…Nuwiq ® (human‐cl rhFVIII, simoctocog alfa, Octapharma AG, Switzerland) is a 4th generation recombinant FVIII (rFVIII) produced in a human cell line with human‐like post‐translational protein processing and without chemical modification or fusion to any other protein . Nuwiq ® is fully sulphated, which ensures a high affinity to circulating von Willebrand factor, contains only human glycans and is therefore devoid of potentially antigenic nonhuman epitopes present in rFVIII derived from hamster cell lines .…”

Perfusion process combining low temperature and valeric acid for enhanced recombinant factor VIII production

“…FVIII is a biopharmaceutical protein used for treatment of Hemophilia A patients, a X-linked bleeding disorder. 15 Depending on the product characteristics (e.g., protein structure), the short half-life can vary between~11 and 22 hr. Additionally, FVIII undergoes a very large number of post-translational modifications.…”

“…12 The full protein is a heterodimer (170-290 kDa) consisting of a light chain (80 kDa) and a heavy chain (90-210 kDa), associated to each other by a metal ion bridge. 15 Due to FVIII instability, industrial processes for rFVIII production are operated in perfusion mode to allow for short residence time in the bioreactor, 16 although a new FVIII product that is under development has been recently reported to be produced in fed-batch mode. 13 Known as a difficult-to-express protein, its production rate is usually 2 to 3 orders of magnitude lower compared to other recombinant proteins.…”