Romiplostim

Romiplostim (rINN, USAN) 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 trials 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 corticosteroids, intravenous immunoglobulin, Rho(D) immune globulin or splenectomy.

Romiplostim treatment is administered by weekly subcutaneous injections, using a variable dosage determined by analysis of the patient's platelet count at the time of treatment. The goal is to maintain the count above 50,000 per cubic millimeter of blood, not to achieve a normal count (defined as 150,000–450,000 per mm3 in most healthy individuals). If a sustained count of 200,000 or higher is achieved for more than two 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.

Romiplostim's effect is to stimulate the patient's megakaryocytes 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.

Clinical efficacy
In well designed, 24-week, Phase III trials, subcutaneous 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.