An investigational recombinant factor VIII (rFVIII) product can safely treat and prevent bleeding in previously treated patients with hemophilia A, according to researchers.
The product, BAX 855, is a pegylated version of ADVATE, a full-length rFVIII product already approved to treat hemophilia A.
BAX 855 was designed to have a longer half-life than ADVATE, thereby allowing for fewer prophylactic infusions without affecting hemostatic efficacy.
Results of a phase 1 study showed that BAX 855 had a longer half-life and mean residence time than ADVATE. And results of a phase 2/3 study showed that twice-weekly prophylactic treatment with BAX 855 lowered the median annualized bleed rate (ABR) when compared to on-demand treatment with BAX 855.
None of the patients who received BAX 855 in either study developed inhibitors, and there were no serious adverse events (AEs) that were considered treatment-related.
Results from both trials were published in Blood. The research was funded by Baxalta, a spin-off of Baxter Healthcare Corporation.
Study characteristics
The phase 1 study included 19 previously treated patients with severe hemophilia A and a median age of 29 (range, 18-60). The patients received single infusions of ADVATE followed by BAX 855 (after a wash-out period) at 30 IU/kg or 60 IU/kg.
In the phase 2/3 trial, researchers evaluated BAX 855 in 137 previously treated patients with hemophilia A. These patients also had a median age of 29 (range, 12-58).
They were assigned to either twice-weekly prophylaxis (40-50 IU/kg, n=120) or on-demand treatment (10-60 IU/kg, n=17) with BAX 855. One hundred and twenty-six patients completed the study.
Pharmacokinetics and safety
In the phase 1 study, the mean residence time was higher with BAX 855 than with ADVATE—1.4-fold higher in the 30 IU/kg arm and 1.5-fold higher in the 60 IU/kg arm. The mean half-life was higher with BAX 855 as well—1.4-fold higher in the 30 IU/kg arm and 1.5-fold in the 60 IU/kg arm.
Results were similar in the phase 2/3 trial.
None of the subjects in the phase 1 study experienced a serious AE after their single infusion of BAX 855. Eight patients experienced a total of 11 non-serious AEs, none of which were considered related to BAX 855.
In the phase 2/3 study, there were 171 AEs in 73 patients who received BAX 855 for about 6 months. There were 7 AEs (occurring in 6 patients) that were considered possibly related to BAX 855. These included diarrhea, nausea, headache, and flushing.
There were 5 serious AEs (occurring in 5 patients) that were not considered treatment-related. These included osteoarthritis, herpes zoster infection, humerus fracture, neuroendocrine carcinoma, and muscle hemorrhage.
Efficacy: Prophylaxis and on-demand
The researchers only assessed the efficacy of BAX 855 prophylaxis and on-demand treatment in the phase 2/3 study.
Patients received a median dose of 44.6 IU/kg per prophylactic infusion. The mean reduction in dosing frequency from pre-study prophylaxis was 26.7%, and 70.4% of patients were able to reduce the frequency of dosing by 30% or more. This is roughly equivalent to at least 1 less prophylactic infusion per week.
Patients who received prophylaxis had a 90% reduction in ABR compared to those who received on-demand treatment. The median ABR was 1.9 in the prophylactic arm and 41.5 in the on-demand arm.
The ABRs for joint bleeds or spontaneous/unknown bleeds were both 0 in the prophylactic arm, compared to 38.1 and 21.6, respectively, in the on-demand treatment arm.
Patients who received on-demand treatment were given a median dose of 30.87 IU/kg per episode and 29.19 IU/kg for the maintenance of hemostasis.
Of the 518 bleeding episodes reported during the study, 95.9% were treated with 1 or 2 infusions of BAX 855. The mean number of infusions required to treat a bleeding episode was 1.2.
