Turoctocog alfa

Inhibitor development is a primary concern for pediatric patients with hemophilia A (HA) undergoing recombinant factor VIII (rFVIII) therapy, yet relevant research is lacking. We aimed to compare the efficacy and safety of standard (SHL) and extended half-life (EHL) rFVIII products in previously treated (PTPs) and untreated (PUPs) pediatric patients with HA.

Following PRISMA guidelines, we searched clinical studies from PubMed, Embase, and Cochrane Library. Data were extracted and a single-arm meta-analysis was performed.

This systematic review included 16 studies involving 1145 patients. Three studies reported changes in annual bleeding rate (ABR); their results displayed no statistically significant difference in ABR changes in pediatric patients with HA after rFVIII treatment. Ten studies reported inhibitor development, nine focused on PUPs. Here, EHL rFVIII showed a proportion of inhibitors at 27.5% (95% confidence interval [CI] 22.6%; 32.6%), and third-generation SHL rFVIII showed a proportion of inhibitors at 36.4% (27.2%; 46.2%), with a high-titer proportion of 20.9% (12.9%; 30.3%) for the latter. Both SHL rFVIII (octocog alfa) and EHL rFVIII (rurioctocog alfa pegol) presented low proportions of inhibitor development. Octocog alfa exhibited the lowest high-titer inhibitor incidence, marked at 12.7% (5.3%; 24.5%). Eleven studies addressed adverse events (AEs), with octocog alfa showing low reported treatment-related AEs at a proportion of 14.5% (6.5%; 26.7%).

Our analysis revealed that both octocog alfa and rurioctocog alfa pegol showed low inhibitor development, with octocog alfa having few treatment-related AEs. Regular monitoring for inhibitors during rFVIII therapy is important.

Hemophilia A (HA) is an inherited condition that is characterized by a lack of coagulation factor VIII (FVIII), which is needed for blood clotting. To produce Recombinant Factor VIII (rFVIII) for treatment, innovative methods are required. This study presents a thorough examination of the genetic engineering and biotechnological methods that are essential for the production of this complex process. Multiple host cells, such as animal, microbial, and human cell lines, are examined. Cultivating genetically modified cells enables the production of rFVIII, with further changes after protein synthesis, such as glycosylation, taking place in eukaryotic cells to guarantee correct folding. The extraction and purification of rFVIII require advanced methods, including affinity chromatography, to improve the purity of the protein. The purified protein undergoes rigorous quality control, which includes Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis (SDSPAGE) analysis, to assess its identity, purity, and functioning. The scalability of this approach allows for the synthesis of significant amounts of rFVIII for therapeutic purposes. Optimization strategies include modifying B-Domain-Deleted (BDD) FVIII, including introns in FVIII Complementary DNA (cDNA) sequences to boost synthesis and storage, and making changes to chaperone-binding areas to optimize protein release. Furthermore, the search for a modified form of FVIII that has a longer duration of action in the body shows potential for enhancing the effectiveness of synthetic FVIII and progressing the treatment of hemophilia A. Future research should focus on improving the treatment of hemophilia A by developing a variant of FVIII that has increased stability and reduced immunogenicity.