How BAX 855 is manufactured
BAX 855 (or rurioctocog alfa pegol) is a PEGylated molecule of full-length recombinant factor VIII (FVIII) produced in Chinese hamster ovary (CHO) cells. It is manufactured by attaching a PEG molecule (with a molecular weight of 20 kDa) to Advate, which is the recombinant factor VIII already approved to treat hemophilia A.
BAX 855 retains all the physiological properties of FVIII except binding to lipoprotein receptor-related protein (LRP), which helps clear them from circulation; clearing factor VIII from the kidneys occurs through interactions with low-density LRP, primarily in the liver. This gives the PEGylated molecule a prolonged half-life. In humans, the mean half-life is reported to be 18 hours, about 1.5 times that of standard recombinant FVIII molecules.
Clinical studies with BAX 855
A Phase 1 clinical trial (NCT01599819) assessed the safety and pharmacokinetics of BAX 855 in 19 patients with severe hemophilia A. This was followed by a pivotal Phase 2/3 trial (NCT01736475) in 137 previously treated patients with severe hemophilia A — ages 12 to 65 — to evaluate the safety, efficacy and pharmacokinetics of BAX 855 administered twice weekly as a preventative or on-demand treatment. This trial showed that the mean half-life of BAX 855 ranged between 14.3 and 16.0 hours, or 1.4 times longer than that of Advate. The median annualized bleed rate (ABR) on prophylaxis was 1.9, with around 40 percent bleed-free patients, while 96 percent of bleeding episodes were successfully treated with one or two infusions. No inhibitory antibodies were detected.
A Phase 3 pediatric trial with BAX 855 (NCT02210091) included 66 previously treated children younger than 12 years old with hemophilia A. It evaluated the immunogenicity, pharmacokinetic profile, safety, efficacy and quality of life during prophylactic treatment. Children received twice-weekly infusions of 50 ±10 IU/kg BAX 855 over a six-month period. The dose could be escalated up to 80 IU/kg according to predefined criteria. Terminal half-life ranged between 12.7 and 13.9 hours, confirming the 1.5-fold prolongation compared to Advate. The total mean ABR was 3.04 with injury-related bleeds as the main contributors to total ABR. Overall, 38 percent of enrolled subjects had zero bleeds during the study, and up to 83 percent of all bleeds were successfully treated with a single injection. No inhibitors were detected during the study, which found a significant reduction in pain as well as an increase in the children’s physical activity.
Another Phase 3 study with BAX 855 (NCT01913405) began in December 2013 to evaluate the drug’s efficacy and safety in previously treated patients undergoing surgery. The trial is ongoing, and an interim analysis has been recently published. This first analysis reported on 15 surgical procedures — 11 of them major — in 15 subjects for which overall intra- and peri-operative hemostatic efficacy was rated as “excellent” in all cases, and no related adverse events were observed.
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