Efficacy and safety of fibrinogen concentrate for on‐demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD. METHODS: Haemostatic efficacy of HFC (Fibryga(®), Octapharma AG) for on‐demand treatment of bleeding and surgical prophylaxis in patients <12 years old was assessed by investigators and an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) based on an objective 4‐point efficacy scale. Maximum clot firmness (MCF; surrogate marker of haemostatic efficacy), single‐dose PK and safety were also assessed. RESULTS: Of 14 patients receiving HFC (median [range] age 6.0 years [1.0–10.0]), eight received HFC for 10 BEs, three for surgical prophylaxis and 13 for PK. The IDMEAC rated haemostatic efficacy as 100% successful for on‐demand BE treatment (95% CI 69.15–100.00) and surgical prophylaxis (95% CI 29.24–100.00). After a mean first dose of 70.78 mg/kg for BEs, mean (±SD) MCF significantly increased from pre‐treatment to 1‐hour post‐infusion (3.3 mm [±1.77]; P = 0.0002), coinciding with haemostatic efficacy. PK parameters were favourable. Two possibly related adverse events occurred, including one serious (portal vein thrombosis). No allergic/hypersensitivity reactions or deaths were observed. CONCLUSION: HFC treatment for on‐demand treatment of BEs and surgical prophylaxis was efficacious for this ultra‐rare paediatric population with congenital afibrinogenaemia and showed a favourable PK and safety profile.