Peginesatide (Omontys): A Comprehensive Monograph on a Promising but Short-Lived Erythropoiesis-Stimulating Agent

Executive Summary

Peginesatide, marketed under the trade name Omontys, was a novel, synthetic peptide-based erythropoiesis-stimulating agent (ESA) developed for the treatment of anemia associated with chronic kidney disease (CKD). Representing a significant departure from existing recombinant protein-based ESAs, its unique molecular architecture featured a PEGylated dimeric peptide with no amino acid sequence homology to endogenous erythropoietin. This design was rationally conceived to offer a convenient once-monthly dosing regimen and to mitigate the risk of antibody-mediated pure red cell aplasia, a known complication of recombinant therapies.

Pivotal Phase III clinical trials, the EMERALD and PEARL studies, successfully demonstrated that once-monthly peginesatide was non-inferior to the standards of care, epoetin alfa and darbepoetin alfa, in maintaining hemoglobin levels within the target range. However, the clinical development program also uncovered a significant safety signal: an increased risk of cardiovascular events and death in the CKD population not on dialysis. This finding led the U.S. Food and Drug Administration (FDA) to grant a restricted approval in March 2012, limiting its use to adult CKD patients on dialysis.

Less than one year after its commercial launch, post-marketing surveillance revealed a rare but catastrophic risk of serious hypersensitivity reactions, including fatal anaphylaxis, occurring shortly after the first intravenous dose. This unforeseen safety issue prompted a nationwide voluntary recall of all product lots in February 2013, followed by the eventual formal withdrawal of its New Drug Application in 2019.