Res Pract Thromb Haemost. 2026 Sep 3;10(6):106939. doi: 10.1016/j.rpth.2026.106939. eCollection 2026 Aug.
ABSTRACT
BACKGROUND: In severe hemophilia A, factor VIII (FVIII) replacement is essential, but FVIII inhibitor development can be serious.
OBJECTIVES: This phase 3, prospective, uncontrolled, open-label, multicenter study (NCT02615691) investigated the immunogenicity, efficacy, and safety of rurioctocog alfa pegol for severe hemophilia A in previously untreated patients.
METHODS: Patients received intravenous prophylaxis (25-50 IU/kg, up to 80 IU/kg, ≥1 dose weekly) and/or on-demand therapy (10-50 IU/kg, up to 80 IU/kg depending on bleed severity). The primary endpoint was FVIII inhibitor incidence (≥0.6 BU/mL [Nijmegen modification of Bethesda assay]) in the full analysis set (patients with ≥100 exposure-days [EDs] or who developed an inhibitor). We present the final data.
RESULTS: Of 146 enrolled patients, 120 received ≥1 dose; all were male, and 55.8% had a family history of hemophilia A. Median (range) age was 9.6 (1.2-60.0) months. In the full analysis set (N = 100), 11 patients developed FVIII inhibitors, and 89 had ≥100 EDs without developing inhibitors (incidence [95% CI], 0.110 [0.056-0.188]). In post hoc analyses, 11 patients developed inhibitors, and 101 and 96 had ≥20 and ≥50 EDs, respectively, without developing inhibitors (incidence [95% CI], 0.098 [0.050-0.169] and 0.103 [0.052-0.177], respectively). Annualized bleeding rates (95% CI) were 1.7 (1.2-2.4), 1.0 (0.7-1.3), and 2.3 (1.7-3.2) for once-weekly prophylaxis, >1× weekly prophylaxis, and on-demand therapy, respectively. Overall, 109 of 120 (90.8%) patients had 745 adverse events; serious adverse events occurred in 47 (39.2%) patients.
CONCLUSION: These data demonstrate a low incidence of FVIII inhibitors among previously untreated patients receiving rurioctocog alfa pegol for severe hemophilia A. Efficacy and safety results were similar to prior reports in previously treated patients.
PMID:42841033 | PMC:PMC13641043 | DOI:10.1016/j.rpth.2026.106939
