Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B
| Autor: | Meng-Yao Lu, Daniel Rubens, Manuel Carcao, Masashi Taki, Susan Kearney, Chunduo Shen, Elena Santagostino |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Asia Time Factors Adolescent Hemorrhage 030204 cardiovascular system & hematology Bethesda unit Hemophilia B Risk Assessment Gastroenterology Drug Administration Schedule Hemostatics Polyethylene Glycols Factor IX 03 medical and health sciences 0302 clinical medicine Risk Factors Internal medicine medicine Clinical endpoint Humans Child Beta (finance) business.industry Incidence (epidemiology) Age Factors Infant Hematology Recombinant Proteins Europe Clinical trial Treatment Outcome 030104 developmental biology Child Preschool North America Patient Safety Long term safety Previously treated business medicine.drug |
| Zdroj: | Thrombosis and Haemostasis. 120:737-746 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | 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- and 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%). |
| Databáze: | OpenAIRE |
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