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JOURNAL ARTICLE

Eltrombopag

Karly P Garnock-Jones, Susan J Keam
Drugs 2009, 69 (5): 567-76
19368418
Eltrombopag, an orally administered, small-molecule non-peptide thrombopoietin receptor agonist, selectively binds to the transmembrane domain of the thrombopoietin receptor on the surface of platelets, megakaryocytes and megakaryocyte precursor cells. The drug acts via the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway to activate megakaryocyte proliferation and differentiation in bone marrow progenitor cells, similar to those observed with endogenous thrombopoietin. Platelet counts are increased as a result of eltrombopag therapy, and the drug has shown good clinical efficacy in adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP) in randomized, double-blind, placebo-controlled, multicentre, phase II dose-finding and phase III trials. After 6 weeks of therapy in the phase III trial, eltrombopag 50 mg/day was associated with a significantly higher response rate (proportion of patients with a platelet count of >or=50 000 cells/microL at day 43; primary endpoint) than placebo in adult patients with chronic ITP. In addition, the proportion of patients with ITP achieving a platelet count of >200 000 cells/microL and discontinuing treatment due to protocol-defined treatment-cessation criteria, was approximately 8-fold higher with eltrombopag than with placebo. Eltrombopag therapy for 6 weeks also significantly decreased the incidence of WHO-defined bleeding compared with placebo. Eltrombopag was generally well tolerated in clinical trials, with an adverse events profile that did not differ significantly from that with placebo.

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