New drugs for familiar therapeutic targets: thrombopoietin receptor agonists and immune thrombocytopenic purpura

European Journal of Haematology. Supplementum
David J Kuter

Abstract

Various agents to treat immune thrombocytopenic purpura (ITP) have been developed on the principle that stimulating the thrombopoietin (TPO) receptor would increase platelet production. First-generation agents--recombinant human thrombopoietin (rHuTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG rHuMGDF)--showed promise, but observations of antibody formation to PEG rHuMGDF led to the discontinuation of development of both agents. Second-generation agents--the TPO peptide mimetics, TPO non-peptide mimetics, and TPO agonist antibodies--have been developed to reduce or eliminate the problem of antigenicity. Clinical studies for some of these agents, such as AMG 531 (romiplosim, Nplate) and eltrombopag (Promacta), are demonstrating their relative safety and efficacy in increasing platelet counts in patients with ITP; AMG 531 and eltrombopag are in late-stage clinical development and are able to stimulate platelet production in patients with ITP. Some differences in safety profiles have been described and are undergoing further study. There are currently seven second-generation TPO receptor agonists that have been reported in the literature, representing the potential advantages--and continuing ...Continue Reading

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Citations

Jan 27, 2009·Current Gastroenterology Reports·Hans L TillmannJohn G McHutchison
Jul 4, 2013·International Journal of Hematology·David J Kuter
Jul 31, 2009·Annual Review of Medicine·David J Kuter
Dec 25, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Sarantos Kyriakopoulos, Cleo Kontoravdi
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Jul 14, 2010·Seminars in Hematology·Hans L Tillmann, John G McHutchison
Nov 26, 2009·Hematology/oncology Clinics of North America·David J Kuter, Terry B Gernsheimer
Sep 26, 2009·Clinical Lymphoma & Myeloma·David J Kuter
Feb 19, 2009·Cytokine & Growth Factor Reviews·Michelle PeruginiRichard J D'Andrea
Jul 27, 2010·American Journal of Hematology·Mary M RuisiJames B Bussel
Dec 19, 2014·British Journal of Haematology·José Ramón González-PorrasTomás José González-López
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Nov 2, 2020·British Journal of Haematology·Anna KhorevaAnna Shcherbina

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