Eltrombopag

Eltrombopag is a medication that has been developed for certain 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 United States and European Union, it is being manufactured and marketed by Novartis under the trade name Promacta in the US and is marketed as Revolade in the EU. Novartis acquired the drug as a part of its asset swap deal with GlaxoSmithKline.
Price for a single dose ranges from £27.50 (25 mg) to £55 (50 mg).
Medical uses.
Eltrombopag was initially approved by the U.S. Food and Drug Administration on November 20, 2008, for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulin therapy, or splenectomy.
Eltrombopag received FDA breakthrough treatment designation in February 2014 for patients with aplastic anemia for which immunosuppression has not been successful. In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia. It has been shown to produce a trilineage hematopoesis in some patients with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts.
On August 24, 2015, the FDA approved eltrombopag (Promacta for oral suspension) for the treatment of thrombocytopenia in pediatric patients 1 year and older with idiopathic thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Development.
In preclinical studies, the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that it increased 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 shown to be effective in two major clinical syndromes: idiopathic thrombocytopenic purpura (ITP) 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 50 mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic ITP.