Introduction: The introduction of recombinant human erythropoietin revolutionized the management of anemia in patients with chronic kidney disease (CKD). In order to circumvent costly recombinant DNA technology, synthetic chemistry techniques were used to manufacture peginesatide, a synthetic peptide that bore no resemblance to previous erythropoiesis-stimulating agents (ESAs), and yet was capable of stimulating erythropoiesis. Compared with other ESAs, peginesatide was deemed to have advantages related to immunogenicity, administration schedule, and cost. Marketing approval was restricted to CKD patients on dialysis because cardiovascular events were more common with peginesatide than with darbepoetin in non-dialysis CKD patients. Unfortunately, unexplained serious adverse drug reactions (sADR) led to quick withdrawal of peginesatide from the market.
Areas covered: This review describes the efficacy and safety of peginesatide in pre-approval clinical trials, sADRs after marketing approval, and lessons learned during its short life-span.
Expert opinion: The case of peginesatide illustrates the difficulties in detecting rare sADRs in trials with limited patient populations and the need for improved pharmacovigilance after marketing approval. However, the need for simpler drug production methods as a result of non-dependence on recombinant DNA techniques and mammalian cell lines remains. Lessons learned during the scientific development of peginesatide can be used in developing other drugs.
Keywords: Adverse drug reactions; anaphylactic; anemia; chronic kidney disease; darbepoetin; epoetin; erythropoiesis-stimulating agent; hemodialysis; hemoglobin; peginesatide; pharmacovigilance.