Dataset Information

Steady-State Plasma Concentrations of Polyethylene Glycol (PEG) are Reached in Children and Adults During Once-Weekly Prophylactic Treatment with Nonacog Beta Pegol (N9-GP).

ABSTRACT: BACKGROUND:Nonacog beta pegol (N9-GP, Refixia®, Rebinyn®) is a human recombinant coagulation factor IX (rFIX) conjugated to a 40-kDa polyethylene glycol (PEG) moiety. PEGylation significantly prolongs the circulation half-life compared with conventional FIX replacement treatments, resulting in higher FIX levels. Although there is extensive clinical experience with PEGylated molecules, the potential for abnormal and/or indefinite PEG accumulation during long-term treatment and the hypothetical impact on long-term safety is still under discussion. AIM:The aim of this study was to examine plasma PEG concentrations in children, adolescents and adults undergoing once-weekly intravenous prophylactic treatment with N9-GP for up to 6.5 years. METHODS:Plasma samples were collected as part of the PARADIGM clinical development programme (PARADIGM 2/4 [NCT01333111 and NCT01395810] and PARADIGM 5 [NCT01467427]). Proton nuclear magnetic resonance (1H-NMR) was used to measure plasma PEG concentrations. RESULTS:Steady-state plasma PEG concentrations were reached approximately 6 months after initiation of weekly prophylactic treatment with 40 IU/kg N9-GP. Mean steady-state plasma PEG concentrations were 5.6 ?g/mL in children???12 years old at enrolment (PARADIGM 5) and 5.3 ?g/mL in adolescents/adults?>?12 years old (PARADIGM 2/4). Plasma PEG concentrations tended to be lower in younger children?

SUBMITTER: Sternebring O

PROVIDER: S-EPMC6875145 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Steady-State Plasma Concentrations of Polyethylene Glycol (PEG) are Reached in Children and Adults During Once-Weekly Prophylactic Treatment with Nonacog Beta Pegol (N9-GP).

Sternebring Ola O Gabel-Jensen Charlotte C Jacobsen Helene H Benie Andrew James AJ Bjørnsdottir Inga I

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20191201 6

<h4>Background</h4>Nonacog beta pegol (N9-GP, Refixia<sup>®</sup>, Rebinyn<sup>®</sup>) is a human recombinant coagulation factor IX (rFIX) conjugated to a 40-kDa polyethylene glycol (PEG) moiety. PEGylation significantly prolongs the circulation half-life compared with conventional FIX replacement treatments, resulting in higher FIX levels. Although there is extensive clinical experience with PEGylated molecules, the potential for abnormal and/or indefinite PEG accumulation during long-term tre ...[more]

PMID: 31549312

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Dataset Information

Steady-State Plasma Concentrations of Polyethylene Glycol (PEG) are Reached in Children and Adults During Once-Weekly Prophylactic Treatment with Nonacog Beta Pegol (N9-GP).

Publications

Steady-State Plasma Concentrations of Polyethylene Glycol (PEG) are Reached in Children and Adults During Once-Weekly Prophylactic Treatment with Nonacog Beta Pegol (N9-GP).

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