Efficacy and Safety of Human Fibrinogen Concentrate in Patients with Congenital Fibrinogen Deficiency: Combined Results of the FORMA-02 and FORMA-04 Clinical Trials

Objective Congenital fibrinogen deficiency (CFD) is a rare disorder characterized by a lack of/low levels of functional fibrinogen. Human fibrinogen concentrate (HFC) is administered for bleeding episode (BE) treatment and for preventing blood loss during surgery in patients with CFD. Here we report combined data from two studies of HFC for on-demand BE treatment and as surgical prophylaxis in adult, adolescent and paediatric patients.

Material and Methods FORMA-02 and FORMA-04 were multicentre, prospective, open-label Phase 3 studies of the efficacy and safety of HFC (Fibryga®, Octapharma) in adult/adolescent and paediatric patients with CFD. Efficacy was assessed by the investigator and adjudicated by an Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC). Adverse events (AEs) were recorded.

Results A total of 39 patients with a median (range) age of 17 years (1–54) received HFC, including 14 paediatric (aged 0–11), 6 adolescent (aged 12–18) and 19 adult patients (aged ≥18).

Thirty-two patients received HFC for treatment of 99 BEs; 97 minor and 4 major. Mean (±SD) total dose per BE was 65.51 mg/kg (±26.47) for adults/adolescents and 93.78 mg/kg (±64.60) for paediatric patients. Overall haemostatic efficacy was rated successful (rating of excellent or good) for 99.0 % of BEs by the IDMEAC ([Table 1]). Efficacy was comparable between the three age subgroups.

Twelve patients received HFC for 15 surgeries (13 minor, 2 major); 3 paediatric and 12 adults/adolescents. Mean (±SD) loading dose prior to surgery was 77.39 mg/kg (±20.22) in adults/adolescents and 78.50 mg/kg (±27.96) in paediatric patients. The two major surgeries required 5 and 7 maintenance infusions and five of the minor surgeries required a median (range) 3 (1–4) maintenance infusions. Overall haemostatic efficacy was rated successful for all surgeries by the investigator and IDMEAC (Table 1).

A total of 101 AEs occurred in 23 patients (59.0 %), including 16 serious AEs in 6 patients. Five AEs in 4 patients were deemed possibly related to treatment. No allergic/hypersensitivity reactions or deaths were observed.

Conclusion Across two Phase 3 clinical trials HFC was efficacious for on-demand treatment of BEs and perioperative prophylaxis in patients with CFD. Efficacy of HFC was comparable for adult, adolescent and paediatric patients, with a favourable safety profile.

Tab 1. Efficacy assessments after HFC treatment

Publication History

Article published online:
18 June 2021