Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B
Journal
Thrombosis and Haemostasis
Journal Volume
120
Journal Issue
5
Pages
737-746
Date Issued
2020
Author(s)
Abstract
Long-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40 IU/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged ? 12 years with HB (FIX activity ? 2%). Primary endpoint: Incidence of anti-FIX inhibitory antibodies (? 0.6 Bethesda Units). We present a 5-year analysis (N = 25, including remaining patients with ? 5 years' follow-up) and compare with a 1-year analysis (? 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years/patient; median total number of N9-GP exposure days: 290.0/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild/moderate in severity; 93.0% were controlled with 1 to 2 N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median/Poisson-estimated mean overall ABR: 0.66/0.99), having decreased from the 1-year analysis (1.00/1.44). Median/Poisson-estimated mean spontaneous ABRs for the 1- A nd 5-year analyses: 0.00/0.45 and 0.00/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for ? 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity ? 2%). ? 2020 Georg Thieme Verlag KG Stuttgart ?? New York.
Subjects
extended half-life; hemophilia B; long-term safety; N9-GP; pediatric clinical trial
SDGs
Other Subjects
macrogol; recombinant blood clotting factor 9; blood clotting factor 9; hemostatic agent; macrogol; recombinant blood clotting factor 9; recombinant protein; abdominal pain; activated partial thromboplastin time; allergic rhinitis; Article; catheter infection; child; clinical article; comparative study; controlled study; contusion; coughing; diarrhea; disease severity; drug efficacy; drug safety; enzyme linked immunosorbent assay; eosinophilia; female; fever; follow up; food poisoning; headache; hemophilia B; hemoptysis; human; incidence; long term care; major surgery; male; nausea; neurologic examination; pharmacokinetic parameters; phase 3 clinical trial; rhinopharyngitis; single blind procedure; single drug dose; steady state; sweat gland disease; thromboembolism; upper respiratory tract infection; urticaria; wheezing; adolescent; age; Asia; bleeding; blood; clinical trial; drug administration; Europe; hemophilia B; infant; multicenter study; North America; patient safety; preschool child; risk assessment; risk factor; time factor; treatment outcome; Adolescent; Age Factors; Asia; Child; Child, Preschool; Drug Administration Schedule; Europe; Factor IX; Hemophilia B; Hemorrhage; Hemostatics; Humans; Infant; North America; Patient Safety; Polyethylene Glycols; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
Publisher
Georg Thieme Verlag
Type
journal article