Objective:
Hemophilia A patients in the US benefit from safe, efficacious, and reliable factor VIII (FVIII) treatments. Novo Nordisk (Bagsværd, Denmark) has developed turoctocog alfa, the first new recombinant (r) FVIII in over a decade.
Methods & Summary:
Turoctocog alfa is a state-of-the-art, B-domain truncated rFVIII product manufactured without the use of human or animal proteins. Truncation of the B- domain was chosen as this domain does not have any function with respect to FVIII clotting activity. Once activated by thrombin, the turoctocog alfa truncated B-domain is cleaved, leaving an active FVIII molecule similar to the endogenous form. Turoctocog alfa is produced in Chinese hamster ovary cells, a reliable, well-established cell line used for the production of recombinant proteins for medicinal purposes. To ensure a homogenous product, isolation of turoctocog alfa uses a five-step purification process; detergent inactivation and concentration, immunoaffinity chromatography, anionic exchange chromatography, nanofiltration (20 nM filter), and gel filtration. The turoctocog alfa production method, together with its molecular structure ensures that all six FVIII tyrosines are fully sulfated. Tyrosine sulfation is important for physiologic binding of FVIII to its co-factor von Willebrand Factor, essential for FVIII stability when in circulation. Turoctocog alfa plasma concentration can be measured using standard one-stage clotting or chromogenic assays without the need for an external standard. Turoctocog alfa has been clinically tested in the guardianTM trials, one of the largest pivotal trial programs undertaken in hemophilia A with over 200 previously treated patients (PTPs) dosed. The safety and efficacy of turoctocog alfa was tested in adults and adolescents (guardianTM1) and children (guardianTM3). For adults and adolescents, turoctocog alfa had a success rate of 85% in management of bleeding episodes, and 89% of bleeds were successfully treated with 1-2 doses. For children, the success rate was 94%, and 95% of bleeds were treated with 1-2 doses. When used for prophylaxis, the median annualized bleeding rate for adults and adolescents was 3.7, while for children it was 3.0. In all surgical procedures performed in guardianTM1 and 3, the success rate was 100% with no safety concern. For both trials, no turoctocog alfa inhibitors were reported, and no safety concerns were observed. A clinical trial in pediatric previously untreated patients (guardianTM4) is ongoing.
Conclusions:
Turoctocog alfa is the new rFVIII treatment from Novo Nordisk, offering an alternative treatment option for patients with hemophilia A.