Immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients with severe hemophilia A: interim results from a phase 3, prospective, multicenter, open-label study

Aim: To determine the immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients (PUPs) with severe hemophilia A (HA).Methods: This prospective, phase 3 study (NCT02615691) was conducted in PUPs, or patients with =2 exposure days (EDs) prior to screening, aged <6 years with severe HA. The primary endpoint was incidence of factor VIII (FVIII) inhibitor development. This protocol-specified interim analysis was conducted after 50 patients had completed =50 EDs without developing FVIII inhibitors or had developed a confirmed inhibitor at any time.Results: Of the enrolled patients, 59/80 (73.8%) received =1 dose of rurioctocog alfa pegol; 54 received prophylaxis, and 35 on-demand treatment. Incidence of inhibitor development was 0.19 (10/52). Total annualized bleeding rate (95% CIs) was 3.2 (2.0-5.0) for patients receiving prophylaxis and 3.2 (1.6-6.3) for on-demand treatment. Hemostatic efficacy of most bleedings was rated as 'excellent' or 'good' after 24 hours (122/131 [93.1%]) and at resolution (161/170 [94.7%]). Five patients received =1 dose of rurioctocog alfa pegol for immune tolerance induction (ITI) and 1 patient was defined as having ITI success. Thirteen patients experienced 14 treatment-related adverse events, including 10 cases of FVIII inhibitor development.Conclusion: This is the first prospective study of rurioctocog alfa pegol for the treatment of PUPs with severe HA.