Pharmacokinetics, Efficacy, and Safety of Nonacog Alfa in Previously Treated Patients with Moderately Severe to Severe Hemophilia B.

ABSTRACT

PURPOSE: Nonacog alfa, a recombinant factor IX (FIX) product, is used for FIX replacement in the treatment and prevention of bleeding events in patients with hemophilia B. This study aimed to provide supplemental pharmacokinetic (PK), efficacy, and safety data for nonacog alfa when administered as part of usual hemophilia care, including on-demand treatment, routine prophylaxis, and surgical prophylaxis. METHODS: Men with previously treated severe or moderately severe hemophilia B (FIX activity ≤2%) were enrolled in this prospective, open-label, nonrandomized, multicenter study. An initial 72-hour PK assessment was performed wherein patients received a single dose of nonacog alfa (75 IU/kg) as an infusion over 10 minutes. A final 72-hour PK assessment was performed at the patient's last visit, after a minimum washout period of 4 days. Correlations between Cmax after the first dose and body weight and body mass index (BMI) were assessed post hoc using Spearman test after evaluating normality. FINDINGS: In total, 23 patients (age, 12-59 years; weight, 44-173 kg; and BMI, 16.3-45.1) with previous exposure to FIX products (median, 460 days; range, 150-2400 days) were enrolled; 21 were evaluable for efficacy. The median number of exposure days per efficacy-evaluable patient in this study was 48 (range, 31-103). The FIX activity profiles showed multiphasic disposition characteristics, with initial mean (SD) PK profiles as follows Cmax, 61.4 (12.5) IU/dL; AUC∞, 1055 (227) IU·h/dL; t½, 23.7 (5.6) hours; and recovery, 0.818 (0.167) IU/dL. Mean plasma FIX activity versus time profiles were essentially identical upon initial exposure and after repeated use (n = 17), and bioequivalence was confirmed. No apparent relationship was observed between Cmax and either body weight (P > 0.1732) or BMI (P > 0.1235). IMPLICATIONS The FIX activity profile after administration of nonacog alfa is predictable and is not altered after repeated exposure during usual hemophilia care. PK parameters are consistent with nonacog alfa use for FIX replacement in on-demand treatment, routine prophylaxis, and surgical prophylaxis in patients with hemophilia B.