Long-term immunogenicity, safety and efficacy of human-cl rhFVIII in previously treated children with severe hemophilia A
J. Bichler1, A. Klukowska2, V. Vdovin3, T. Szczepanski4, I. Dzhunova1, R. Liesner5 (1Lachen, Switzerland, 2Warsaw, Poland, 3Moscow, Russian Federation, 4Katowice, Poland, 5London, United Kingdom)
Bleeding disorders, coagulation and fibrinolytic factors
Time: 17:15 - 18:15
Objective: The study investigated the efficacy and safety of long-term prophylactic treatment with Human-cl rhFVIII (Nuwiq®) in previously treated children with severe haemophilia A.
Methods: This prospective, open-label, uncontrolled, multi-center Phase 3b study was open to children who had completed the predecessor study GENA-03 with at least 50 exposure days (ED) and at least 6 months of treatment. Patients continued prophylaxis with injections every other day or 3 times per week. Inhibitor (Bethesda assay, Nijmegen modification) and non-inhibitory antibody tests (ELISA-based) were performed in a central laboratory at study start, then every 3 months and at study completion. Adverse events were recorded throughout the study.
Results: Informed consent was obtained from the patient/legal guardian(s) prior to any trial-related activity. The study enrolled 49 patients from 10 centers across 6 European countries. Their median (range) age at study start was 6.0 (3.0-13.0) years. They received a total of 27.5 million International Units (IU) with 20,518 injections of Human-cl rhFVIII over a median (range) period of 2.5 (0.8-4.4) years: 19,723 injections were given for prophylaxis, 485 for treatment of bleeding episodes, 261 for surgical prophylaxis and 47 for recovery assessments. The mean (± SD) dose per prophylactic injection was 38.6 ± 6.7 IU/kg. The spontaneous annualized bleeding rate (negative binomial regression) was 0.67 (all bleeds 2.88) compared to 1.36 (all bleeds 3.54) of the same patients in the predecessor study. The majority of bleeding events were traumatic (62.2%). There were 24 surgical procedures (12 minor, 12 major) performed in 14 children. The efficacy was rated as “excellent” for all (100%) documented procedures. Only 2 (<0.01%) injections were connected with adverse drug reactions dyspnea, fever after FVIII injection). No patient developed an inhibitor.
Conclusion: The data suggest that long-term prophylaxis with Human-cl rhFVIII (Nuwiq®) in children is efficacious and has a favourable safety profile.