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Figure 1. Study selection. [dagger] Health economic search terms include: PEGylation/PEGylated; non-PEGylated; economic; economic benefits; cost, cost-offset, cost-effective/cost-effectiveness, cost-utility, cost-savings, cost of treatment; cost drivers; price; budget impact; and quality-adjusted life-year (QALY).
[double dagger] PEG drugs include: PEGylated liposomal doxorubicin, PEGfilgrastim, PEGinterferon-α2a and -2b, PEGaspargase, certoluzimab PEGol, PEGylated epoetin, PEGademase bovine, PEGmisovant, PEGaptanib, PEGamotecan. PEG: Pegylation.
(Figure omitted. See article PDF.)
Pegylation is a process in which one or more molecules of polyethylene glycol (PEG) react with a biomolecule, usually a protein, peptide, small molecule or oligonucleotide. When attached, PEG significantly increases the hydrodynamic radius of a protein. First studied in 1977 [1], PEG is used not only as a drug-delivery technology but also as a drug-modification technology, producing increases in exposure, elimination half-life, maximal serum concentration and decreases in renal clearance and the volume of distribution. Also, receptor- and antibody-mediated clearance mechanisms and proteolysis may be reduced, and potentially, if the PEG is able to block recognition of specific epitopes by the immune system, antigenicity and immunogenicity may be reduced as well. PEG may additionally improve factors benefiting drug product manufacture and storage by increasing the solubility and stability of proteins.
These properties of PEG drugs increase their potency compared with unmodified native molecules, which in comparison exhibit relatively poor stability, short half-life and enzymatic degradation [2]. Thus, these advantages may manifest clinical benefits. For example:
* The longer plasma half-life increases the biologic activity above that of the non-PEG version [3];
* Longer absorption half-life can lead to reduced frequency of administration [4];
* Improved tumor targeting may lead to improved efficacy in oncology [5];
* Less antigenicity and immunogenicity may result in improved tolerability or in increased dosage levels without an increase in the rate and severity of adverse events relative to the non-PEG version [6].
Ten PEG drugs have been approved by the US FDA since 1990. They include PEG liposomal doxorubicin (PLD), PEGfilgrastim (PFIL), PEGinterferon-α2a and 2b (PA 2a and 2b), PEGademase bovine, PEGaspargase (PASP), certoluzimab PEGol (CP), PEG epoetin (PE), PEGmisovant and PEGaptanib. In addition, several PEG drugs -including PEGamotecan (PM) and PEGinterferon β-1a -are in clinical development. Clinical experience with these PEG therapies in diverse therapeutic areas has demonstrated that they offer patients unique benefits, including at...