Watch out for a revival of peginesatide in sports

Abstract

The erythropoietin-mimetic peptide (EMP) peginesatide belongs to the group of erythropoiesis-stimulating agents (ESAs) that are prohibited when misused in sports. Peginesatide is a synthetic pegylated homodimer of two cyclic 21-amino acid chains. It was approved for the treatment of anaemic patients with chronic kidney disease in the USA in 2012, but recalled in 2013 due to prevalent cases of acute severe anaphylactoid reactions and associated fatalities (0.02%). The drug was considered obsolete for athletes and part of the anti-doping scene lost sight of it. However, recent research indicates that the adverse events were not caused by the drug substance, but by the drug product formulated in multi-use vials. These vials contained comparably high levels of subvisible particles. Phenol was identified as a critical component of the drug formulation, which caused the release of histamine from mast cells. Tricky athletes might consider peginesatide a pharmacologically safe ESA in an appropriate formulation. In addition, other EMPs may get a second wind for therapy including misuse in sports. Therefore, it is very important to proceed in developing electrophoretic, immunological, and mass spectroscopic methods for detecting peginesatide and other EMPs in human urine and blood samples. Copyright © 2016 John Wiley & Sons, Ltd.

PEGylated therapeutics in the clinic

“…43,44 According to research performed later, such hypersensitivity reactions are likely caused by subvisible nanoparticles associated with phenol used in the commercialized multi-use vial formulation, rather than the drug substance itself. [45][46][47] PEGylated drugs have been used to treat different types of cancers.…”

“…Omontys™ (peginesatide) was voluntarily recalled by the manufacturers in 2013, because of serious acute hypersensitivity reactions and associated fatalities (0.02%) 43,44 . According to research performed later, such hypersensitivity reactions are likely caused by subvisible nanoparticles associated with phenol used in the commercialized multi‐use vial formulation, rather than the drug substance itself 45–47 …”

Annual banned‐substance review: Analytical approaches in human sports drug testing

“…Irrespective of the extent of the performance‐enhancing potential of ESAs, continuous optimization of doping controls for EPO and related substances are essential for comprehensive anti‐doping enforcement especially as there is always the potential threat of a renaissance in obsolete drugs such as peginesatide or erythropoietin mimetic peptides (EMPs) and biosimilars which might present slightly different structures than their corresponding predecessors. As outlined by Okano et al, selected biosimilars of rhEPO and the novel erythropoiesis stimulating protein (NESP) were found to comprise an additional C‐terminal arginine moiety .…”