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

Authors: Djambas Khayat, C; Lohade, S; D’Souza, F; Shamanur, LG; Zekavat, OR; Kruzhkova, I; Schwartz, B; Solomon, C; Knaub, S; Peyvandi, F.

Affiliations: Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon ; Sahyadri Specialty Hospital, Pune, India ; St. John’s Medical College Hospital, Bangalore, India; S.S Institute of Medical Science and Research Center, Davangere, India; Hematology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; Research & Development Department, Octapharma, Lachen, Switzerland; Clinical Research & Development, Octapharma, Paramus, NJ, USA; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy.

Publication: Haemophilia; 2021; 27. 283–292

Abstract: 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 favorable. 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 favorable PK and safety profile.