Healing / Recovery
    Phase 3 Trials

    PEG MGF

    Also known as: Omontys, Affymax EPO mimetic, AF37702

    Peginesatide is a synthetic PEGylated peptide-based erythropoiesis-stimulating agent (ESA) that activates the erythropoietin (EPO) receptor to stimulate red blood cell production. Marketed briefly as Omontys, it was designed as an alternative to recombinant EPO products for treating anemia in chronic kidney disease. Unlike traditional ESAs, peginesatide is a synthetic dimeric peptide with no structural homology to erythropoietin, developed to avoid anti-EPO antibody-mediated pure red cell aplasia. It received FDA approval in March 2012 but was voluntarily withdrawn in February 2013 following reports of serious hypersensitivity reactions including fatal anaphylaxis. Research interest continues in modified formulations and the synthetic peptide EPO agonist concept remains scientifically valid.

    View Product

    Research overview

    Peginesatide, also known as Omontys or AF37702, represents a novel synthetic peptide approach to erythropoietin receptor activation in hematology research. This compound consists of two identical 21-amino-acid synthetic peptide chains connected by a polyethylene glycol (PEG) moiety, creating a dimeric structure with unique properties for laboratory investigations. Despite having no sequence homology to endogenous erythropoietin, peginesatide demonstrates remarkable specificity in binding to and activating the EPO receptor (EPOR) on erythroid progenitor cells within bone marrow tissue in research models. Upon receptor binding, the compound triggers the JAK2-STAT5 signalling cascade, a critical pathway that promotes the survival, proliferation, and differentiation of erythroid precursors into mature red blood cells. The PEGylation modification serves a dual purpose in research applications. Firstly, it significantly extends the compound's half-life, enabling monthly experimental parameters schedules in experimental designs. Secondly, the lack of structural similarity to natural EPO was designed to prevent cross-reactive antibody formation, making it valuable for studies examining immune responses to erythropoiesis-stimulating agents. Clinical research data from the PEARL and EMERALD Phase 3 programmes demonstrated non-inferiority to epoetin alfa in maintaining haemoglobin levels in chronic kidney disease models. However, post-marketing surveillance revealed unexpected serious anaphylactic reactions, leading to voluntary withdrawal in 2013. Despite these safety concerns, the research provided crucial proof-of-concept data for synthetic peptide-based EPO receptor agonism, contributing valuable insights to hematology research and peptide design strategies.

    Mechanism of action

    Peginesatide consists of two identical 21-amino-acid synthetic peptide chains linked by a PEG moiety. Despite having no sequence homology to endogenous erythropoietin, the dimeric peptide binds to and activates the EPO receptor (EPOR) on erythroid progenitor cells in bone marrow. This triggers the JAK2-STAT5 signalling cascade, promoting survival, proliferation, and differentiation of erythroid precursors into mature red blood cells. PEGylation extends the half-life allowing monthly administration. The lack of structural similarity to EPO was intended to prevent cross-reactive antibody formation.

    Frequently asked questions