Analysis of fibrinogen concentrate pharmacokinetics and dosing for bleeds and surgery in adults, adolescents, and children with congenital afibrinogenaemia and hypofibrinogenaemia

INTRODUCTION: Congenital afibrinogenaemia and hypofibrinogenaemia are rare coagulation disorders where clotting is impaired due to a lack of fibrinogen. Consequent bleeding episodes (BEs) are treated using human fibrinogen concentrate (HFC). AIM: This post‐hoc analysis compared HFC pharmacokinetics (PK) and dosing between patient age groups and defined the in vivo recovery (IVR) for children with a‐ and hypofibrinogenaemia. METHODS: The analysis used data from the FORMA‐01 (Phase 2), FORMA‐02 and FORMA‐04 (Phase 3) multinational, prospective, open‐label studies in patients with a‐ and hypofibrinogenaemia. HFC PK in adults/adolescents (≥12 years; FORMA‐01) and children (<12 years; FORMA‐04) was examined. Haemostatic efficacy in BE treatment and perioperative prophylaxis was examined in FORMA‐02 and FORMA‐04 using an objective 4‐point scale, with success defined as excellent/good. RESULTS: Median (range) age was 23 years for FORMA‐01 (12–53; n = 22), 26.5 years for FORMA‐02 (12–54; n = 25), and 6 years for FORMA‐04 (1–10; n = 13). Mean PK parameters were lower for children (AUC, C(max), IVR; p = .02), while clearance was higher. Median (range) total dose of HFC for all BEs was 59.41 mg/kg (32.12–273.80) in adults/adolescents and was 24% higher (ns) in children at 73.91 mg/kg (47.45–262.50). Treatment was successful in 98.9% of the 89 BEs in adults/adolescents and in 100% of the 10 BEs in children, with comparable results for perioperative prophylaxis. CONCLUSION: As expected, HFC PK differed between adults/adolescents and children. However, with the higher doses given to children, HFC showed similar efficacy across age groups. Dose adaptation based on age groups appears recommendable.