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Three classes of agents that stimulate platelet production are being developed. These all bind to and stimulate the thrombopoietin (TPO) receptor: TPO peptide mimetics (e.g., AMG 531), TPO nonpeptide mimetics (e.g., AKR-501, eltrombopag), and TPO-agonist antibodies (genetically modified to create small bivalent fragments called minibodies; Blood 2007; 109:4607). All of the agents raise platelet counts in animal models; two, AMG 531 and eltrombopag, are currently in clinical development. AMG 531, when injected weekly for 6 weeks, significantly increased platelet counts in 12 of 16 patients with immune thrombocytopenic purpura (ITP; N Engl J Med 2006; 355:1672).
In a phase 1 dose-finding study of eltrombopag, conducted by industry employees, t…