Romiplostim, sold under the brand name Nplate among others, is a
fusion protein
Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' r ...
analog of
thrombopoietin
Thrombopoietin (THPO) also known as megakaryocyte growth and development factor (MGDF) is a protein that in humans is encoded by the ''THPO'' gene.
Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the pro ...
, a
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
that regulates
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
production.
Indications and Marketing
The drug was developed by
Amgen
Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical Corporation, company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen was esta ...
through a restricted usage program called NEXUS.
[ During development and ]clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s the drug was called AMG531.orphan drug
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases.
The assignment of ...
by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) in 2003, as the chronic ITP population in the USA is under 200,000 (the chronic adult ITP population in the USA is thought to be around 60,000, with women outnumbering men by a factor of two). The wholesale cost of romiplostim if administered weekly is currently estimated at US$55,250 per year.
On August 22, 2008, the FDA approved romiplostim as a long-term treatment for chronic ITP in adults who have not responded to other treatments, such as corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s, intravenous immunoglobulin
Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
, Rho(D) immune globulin
Rho(D) immune globulin (RhIG) is a medication used to prevent RhD isoimmunization in mothers who are RhD negative and to treat idiopathic thrombocytopenic purpura (ITP) in people who are Rh positive. It is often given both during and followi ...
or splenectomy
A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of ...
.[ Freely available with registration.]
Treatment regimen
Romiplostim treatment is generally administered at weekly intervals via subcutaneous injection
Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...
. Prior to injection, a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
(CBC) is obtained, as the dosage is dependent on the individual's body weight and platelet count
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
at the time of treatment. The goal of treatment is to maintain the count above 50,000 per cubic millimeter (mm3) of blood, not to achieve a normal count—defined as 150,000–450,000 per mm3 in most healthy individuals. If a count of 200,000 or higher is achieved for two consecutive weeks a reduced dose is administered or treatment is suspended until the count decreases below 200,000. Discontinuation of romiplostim is usuallly done by tapered dose, as abruptly stopping treatment can lead to rebound thrombocytopenia.
Clinical efficacy
In well designed, 24-week, Phase III trials, romiplostim was significantly more effective than placebo in achieving the primary endpoint of a protocol-defined durable platelet response in nonsplenectomized or splenectomized adults with chronic immune thrombocytopenic purpura.
Side-effects
Romiplostim's effect is to stimulate the patient's megakaryocyte
A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In hum ...
s to produce platelets at a more rapid than normal rate, thus overwhelming the immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
's ability to destroy them. As doing so involves changes to the bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
chemistry, a number of potentially serious side-effects
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
may develop, including death, myalgia
Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...
, joint and extremity discomfort, insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, thrombocytosis
Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. ...
, which may lead to potentially fatal clot
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
s, and bone marrow fibrosis, the latter of which may result in an unsafe decrease in the red blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and plat ...
.
Experimental treatment of acute radiation syndrome
Romiplostim may be used to treat acute radiation syndrome.
References
External links
*
{{Portal bar , Medicine
Antihemorrhagics
Orphan drugs
Thrombopoietin receptor agonists