The safety and efficacy of N8-GP (turoctocog alfa pegol) in previously untreated pediatric patients with hemophilia A.

N8-GP (turoctocog alfa pegol; Esperoct®) is a recombinant, glycoPEGylated, extended half-life, factor VIII replacement product. Here, we examined the immunogenicity, safety, and efficacy of N8-GP in previously untreated patients (PUPs). pathfinder6 (NCT02137850) is an ongoing, open-label, phase 3 trial that enrolled PUPs with severe hemophilia A, <6 years old. The primary endpoint was the incidence of FVIII inhibitors (≥0.6 Bethesda units [BU]). Eighty patients received ≥1 N8-GP dose and were included in this analysis with ≥50 patients having ≥50 exposure days to N8-GP. The inhibitor incidence was 29.9% (14.9% high-titer ≥5 BU). Sixty-five patients received N8-GP prophylaxis for an average of 2.17 years with a median annualized bleeding rate (interquartile range) of 1.42 (0.76; 3.13), and a 90.5% hemostatic success rate. Temporarily decreased incremental recovery (IR; defined as ≥2 consecutive measurements of IR <0.6 (IU/dL)/(IU/kg) but no inhibitors) was observed in 17 patients within 5 exposure days to N8-GP and had a strong temporal correlation with anti-PEG IgG antibody titers. IR returned within the expected range with continued N8-GP dosing. During the period of decreased IR, hemostatic response was similar to the overall trial population, and no hypersensitivity related to N8-GP or unexpected new adverse events were reported. N8-GP prophylaxis was efficacious for the prevention and treatment of bleeding episodes in PUPs with severe hemophilia A. The inhibitor incidence was 29.9%. All patients with temporarily decreased IR continuing on N8-GP dosing returned within the expected range and had no evident lack of efficacy.