Current and Upcoming Erythropoiesis-Stimulating Agents, Iron Products, and Other Novel Anemia Medications

Abstract

Treatment for anemia has come a long way in the last 20 years since the first recombinant human erythropoietins were licensed for the management of anemia in chronic kidney disease. The first-generation epoetins were succeeded by the development and production of a longer-acting erythropoietin (EPO) analog, darbepoetin alpha, which allowed less frequent dosing, usually once weekly or once every 2 weeks. More recently, another EPO-related molecule has been manufactured called Continuous Erythropoietin Receptor Activator with an even longer half-life, and although for patent reasons this is not available in the United States, it is licensed and is already being used in Europe. Other molecules are in development or are becoming licensed in Europe, including biosimilar epoetin products/follow-on biologics, and elsewhere in the world there are cheaper-production "copy" epoetins. Indeed, it is estimated that up to 80 such products may be sold in countries with less stringent regulatory control of pharmaceutical products. Two different biosimilar epoetins have already been licensed in Europe, one under 2 different brand names and one under 3 different brand names, and others may follow. Hematide is a synthetic peptide-based EPO receptor agonist that, interestingly, has no structural homology with EPO, and yet is still able to activate the EPO receptor and stimulate erythropoiesis. This agent is currently in phase III clinical trials. Research continues for orally active antianemic therapies, and several strategies are being investigated, although none is imminently available. Two new intravenous iron preparations have recently been developed, one in the United States (Ferumoxytol; AMAG Pharmaceuticals, Inc., Cambridge, MA) and one recently licensed in Europe (ferric carboxymaltose [Ferinject; Vifor Pharma, Zurich, Switzerland]). In conclusion, the development of effective therapies for the treatment of anemia has been a highly active field, both scientifically and economically, over the last two decades.