Eltrombopag

Eltrombopag (rINN, codenamed SB-497115-GR) is a medication that has been developed for conditions that lead to thrombocytopenia (abnormally low platelet counts). It is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. Designated an orphan drug in the USA and European Union, it is being manufactured and marketed by GlaxoSmithKline under the trade name Promacta in the USA and will be marketed as Revolade in the EU. Eltrombopag was approved by the U.S. Food and Drug Administration on November 20, 2008.

Development
In preclinical studies, the compound was shown to interact selectively with the thrombopoeitin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that administration could increase platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.

Clinical trials
Eltrombopag has been studied, and shown to be effective, in two major clinical syndromes: idiopathic thrombocytopenic purpura and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment). After 6 weeks of therapy in a phase III trial, eltrombopag 50mg/day was associted with a significantly higher resonse rate than placebo in adult patients with chronic ITP.