First report on the safety and efficacy of an extended half‐life glycoPEGylated recombinant FVIII for major surgery in severe haemophilia A

Abstract

BackgroundN8‐GP (turoctocog alfa pegol) is an extended half‐life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia A patients.AimThis is a planned interim analysis of pathfinder™3, an international, open‐label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8‐GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years.MethodsSixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1–6, and once for days 7–14. Primary endpoint was N8‐GP haemostatic efficacy, assessed after completion of surgery using a four‐point scale (‘excellent’, ‘good’, ‘moderate’, ‘none’).ResultsHaemostasis was successful (rated ‘excellent’ or ‘good’) on completion of surgery in 17 (94.4%) procedures and rated as ‘moderate’ (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8‐GP dose (20.7 IU kg−1). In the postoperative period, three bleeds occurred (one during days 1–6; two during days 7–14); all were successfully treated with N8‐GP. Mean N8‐GP consumption on day of surgery was 80.0 IU kg−1; patients received a mean of 1.7 doses (median: 2, range: 1–3). No safety concerns were identified.ConclusionThe data showed that N8‐GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half‐lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge.