The Cost Offsets and Cost-Effectiveness Associated With Pegylated Drugs

A Review of the Literature

Russell Becker; Carole Dembek; Leigh Ann White; Louis P Garrison

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2012;12(6) 

In This Article

Abstract and Introduction

Abstract

Pegylation (PEG) is used as both a drug-delivery and a drug-modification technology in ten drugs approved by the US FDA. Benefits of PEG drugs can include increased plasma half-life, longer absorption, improved tumor targeting and less antigenicity and immunogenicity. Clinical benefits of PEG drugs over non-PEG drugs may include reduced administration, improved efficacy, improved tolerability, and decreased severity and incidence of adverse events. This study reviews 37 economic literature publications featuring PEG drugs versus non-PEG versions. PEG drugs showed some reductions in overall costs resulting from various offsets including fewer administrations, lower adverse event treatment costs, reduced disease complication costs or reduced inpatient/outpatient costs. Of the 18 cost–effectiveness studies reviewed, 17 of them found PEG drugs to be cost effective versus the non-PEG drugs. Cost offsets and cost–effectiveness of PEG drugs have been demonstrated in multiple studies across various therapies, indications and country settings, and the results have been found to be stable when key parameters were varied in analyses. Further studies are needed to assess the potential for cost savings and cost–effectiveness for new PEG therapies in development.

Introduction

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-α 2a 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 least comparable efficacy and more convenient dosing, while maintaining the safety and tolerability of the parent molecule.[2]

PEG drugs have been found to have clinical benefits similar to or better than their non-PEG native counterparts. PASP has demonstrated equivalent efficacy compared to the non-PEG version asparaginase (ASP) but with fewer administrations. Allergic reactions, premedication dosing and skin tests are all reduced as well.[7] PLD has demonstrated improved response rates and reduced incidence of neutropenia in the treatment of Kaposi's sarcoma[8–10] and has shown reduced adverse events with fewer administrations in multiple myeloma treatment.[11] In multiple cancer indications, PFIL has been shown to reduce the incidence of febrile neutropenia versus filgrastim, while requiring fewer administrations.[12–14] In the treatment of hepatitis B and C, PA 2a and 2b have shown sustained virological response (SVR) and reduced disease complications compared to the non-PEG versions.[15–17] PE has also shown improved efficacy over the non-PEG version while requiring fewer administrations.[18] Other approved PEG drugs have demonstrated clinical benefits as well but do not have non-PEG versions available for comparison.

Given the documented clinical benefits of PEG therapies, there is interest in learning when these clinical benefits translate into economic benefits. Improved efficacy or lower costs may translate into PEG therapies being more cost effective than their non-PEG counterparts. For example, since several PEG drugs can be given less frequently, drug administration costs may be decreased. Also, reductions in adverse events and improvements in efficacy may lead to reduced resource utilization and costs as well.

The published literature summarizing the benefits of PEG consists of a few articles that focus solely on the clinical benefits.[2,3] To date, there have been no articles discussing the general economic benefits of PEG, nor have any studies been conducted researching trends regarding the economic impact of PEG drugs. Only individual economic studies of individual PEG drugs have been published thus far.

To begin to address these issues, this study reviews the current published economic literature featuring PEG drugs. The study seeks to improve the existing understanding of the economic impact of PEG, and specifically, the cost offsets and cost–effectiveness associated with PEG drugs. The review also attempts to better understand both the magnitude of PEG's economic benefit and consider commonalities across various therapeutic areas and countries in terms of the economic drivers of any benefits.

processing....