Romiplostim
Encyclopedia
Romiplostim is a fusion protein
analog of thrombopoietin
, a hormone
that regulates platelet
production. The drug was developed by Amgen
and is marketed under the trade name Nplate through a restricted usage program called NEXUS. During development and clinical trial
s the drug was called AMG531.
Romiplostin is indicated as a potential treatment for chronic idiopathic (immune) thrombocytopenic purpura (ITP). Romiplostim was designated an orphan drug
by the U.S. Food and Drug Administration (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
s, intravenous immunoglobulin
, Rho(D) immune globulin
or splenectomy
.
. Prior to injection, a complete blood count
(CBC) is obtained, as the dosage is dependent on the individual's body weight and platelet count 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 must be approached with great caution, as a rapid decrease in the platelet count may occur, possibly leading to bleeding diathesis
.
s to produce platelets at a more rapid than normal rate, thus overwhelming the immune system
's ability to destroy them. As doing so involves changes to the bone marrow
chemistry, a number of potentially serious side-effects
may develop, including myalgia
, joint and extremity discomfort, insomnia
, thrombocytosis
, which may lead to potentially fatal clots, and bone marrow fibrosis
, the latter which may result in an unsafe decrease
in the red blood count.
Fusion protein
Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...
analog of thrombopoietin
Thrombopoietin
Thrombopoietin also known as megakaryocyte growth and development factor is a protein that in humans is encoded by the THPO gene....
, a 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...
that regulates 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...
production. The drug was developed by Amgen
Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
and is marketed under the trade name Nplate through a restricted usage program called NEXUS. During development and clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s the drug was called AMG531.
Romiplostin is indicated as a potential treatment for chronic idiopathic (immune) thrombocytopenic purpura (ITP). Romiplostim was 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...
by the U.S. Food and Drug Administration (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
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s, intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
, Rho(D) immune globulin
Rho(D) Immune Globulin
Rho Immune Globulin is a medicine given by intramuscular injection that is used to prevent the immunological condition known as Rhesus disease...
or splenectomy
Splenectomy
A splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
.
Treatment regimen
Romiplostim treatment is generally administered at weekly intervals via subcutaneous injectionSubcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...
. Prior to injection, a complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
(CBC) is obtained, as the dosage is dependent on the individual's body weight and platelet count 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 must be approached with great caution, as a rapid decrease in the platelet count may occur, possibly leading to bleeding diathesis
Bleeding diathesis
In medicine , bleeding diathesis is an unusual susceptibility to bleeding mostly due to hypocoagulability, in turn caused by a coagulopathy . Several types are distinguished, ranging from mild to lethal...
.
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 megakaryocyteMegakaryocyte
The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes , which are necessary for normal blood clotting...
s to produce platelets at a more rapid than normal rate, thus overwhelming the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
's ability to destroy them. As doing so involves changes to the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
chemistry, a number of potentially serious side-effects
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
may develop, including myalgia
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, joint and extremity discomfort, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, thrombocytosis
Thrombocytosis
Thrombocytosis is the presence of high platelet counts in the blood, and can be either primary or reactive...
, which may lead to potentially fatal clots, and bone marrow fibrosis
Myelofibrosis
Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
, the latter which may result in an unsafe decrease
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
in the red blood count.