Eltrombopag
Encyclopedia
Eltrombopag 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.
and increased proliferation and differentiation of megakaryocyte
s. 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.
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 associated with a significantly higher response rate than placebo in adult patients with chronic ITP.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
that has been developed for conditions that lead to thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(abnormally low platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
counts). It is a small molecule agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
of the c-mpl (TpoR) receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, which is the physiological target of the hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
thrombopoietin
Thrombopoietin
Thrombopoietin also known as megakaryocyte growth and development factor is a protein that in humans is encoded by the THPO gene....
. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
and Ligand Pharmaceuticals. Designated an orphan drug
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
in the USA and European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
, it is being manufactured and marketed by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
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 pathwayJAK-STAT signaling pathway
The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell. The JAK-STAT system is a major signaling alternative to the second...
and increased proliferation and differentiation of megakaryocyte
Megakaryocyte
The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes , which are necessary for normal blood clotting...
s. 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 purpuraIdiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura is the condition of having an abnormally low platelet count of no known cause . As most incidents of ITP appear to be related to the production of antibodies against platelets, immune thrombocytopenic purpura or immune thrombocytopenia are terms also used to...
and cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
due to hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
(in which low platelet counts may be a contraindication for interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
treatment).
After 6 weeks of therapy in a phase III trial, eltrombopag 50mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic ITP.