Peginesatide

Introduction: Erythropoiesis-stimulating agents (ESAs) are the mainstay of treatment in anemic chronic kidney disease (CKD) patients. A tailored ESA therapy should combine maximal efficacy and safety with greatest convenience in dosing. Peginesatide, recently approved in the US for once-monthly dosing in adult patients on dialysis, is a promising novel PEGylated erythropoietin-mimetic peptide for the treatment of renal disease-induced anemia. Areas covered: Published animal and human studies that evaluated the pharmacodynamics, pharmacokinetics, clinical efficacy and safety of peginesatide were critically analyzed. Expert opinion: Peginesatide has a well-studied pharmacological and immunological profile, and latest published data favor the use of peginesatide in place of epoetin in dialysis patients. A more detailed evaluation of its safety profile particularly in trials with CKD patients not requiring dialysis is urgently needed, as peginesatide could be a perfect treatment solution for these patients. In addition, clinical long-term data and results from supplemental studies, e.g., with the PEGylated continuous erythropoietin receptor activator as comparator, should briefly follow. The fate of peginesatide on the highly competitive ESA market is currently not predictable and depends on safety and efficacy results of upcoming trials as well as finally on market and price policy.

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.