Romiplostim (Nplateâ„¢ | Amgen, Inc.), a novel thrombopoiesis-stimulating peptibody protein, has been granted the US FDA approval for the long-term treatment of thrombocytopenia (low blood platelet counts) in adults with chronic immune thrombocytopenic purpura (ITP). Romiplostim, the first and only FDA-approved platelet producer, raises and maintains the blood platelet counts, offering a new therapeutic approach for this rare, chronic hematological disorder.
A team of researchers led by David J Kuter, Director, Center for Hematology, Massachusetts General Hospital, Boston, Massachusetts (The Lancet, 2008) conducted double-blind, two parallel, phase III studies to assess the long-term safety and efficacy of romiplostim in treating ITP. Splenectomized (n=63) and non-splenectomized ITP patients (n=62) with a mean platelet count of ≤30×109/L were randomized (2:1) to receive once-weekly, subcutaneous injections of either romiplostim (n=42 in splenectomized study and n=41 in non-splenectomized study) or placebo (n=21 in both studies), for a period of 24 weeks. The drug dosages were adjusted to sustain platelet counts between 50×109/L to 200×109/L. Durable platelet response, defined as the blood platelet count of ≥50×109/L, for a duration of six weeks or more, of the last eight weeks of the treatment period, was used to measure the efficacy of the drug.
The study findings showed that the overall platelet response rate (durable or transient platelet response) was documented in 88% of non-splenectomized and 79% of splenectomized patients treated with romiplostim, against 14% of the patients administered with placebo. Platelet counts of ≥50×109/L were reported in all romiplostim-treated patients for a mean of 13.8 weeks against 0.8 weeks in the placebo group, and 87% of romiplostim-treated patients discontinued or reduced the use of concurrent medications when compared to 28% of the placebo group. It was also evident that the adverse events developed were similar in both the drug-treated and placebo group and no antibodies were detected against the drug.
Romiplostim is a novel, genetically engineered, Fc-peptide fusion protein (peptibody) molecule, which mimics thrombopoietin (TPO), a naturally available hormone that regulates the production of platelets by bone marrow megakaryocytes. The drug when administered subcutaneously stimulates the TPO receptor (cMpl) and activates the intracellular transcription pathways essential for the growth and maturation of bone marrow cells, resulting in increased platelet production. Some of the common adverse events associated with the drug include dizziness, headache, arthralgia, insomnia, myalgia, paresthesia and dyspepsia. The drug may also cause certain uncommon serious adverse reactions such as increased bone marrow reticulin, bone marrow fibrosis, worsening of blood cancer and high platelet counts, which may increase the chances of blood clots. Romiplostim was given an orphan drug status by the US FDA in 2003 and European Agency for the Evaluation of Medicinal Products (EMEA) in 2005.
Chronic thrombocytopenic purpura, also known as immune thrombocytopenic purpura, is a rare but serious autoimmune disorder characterized by low blood platelet counts. The platelet count drops down to abnormally low levels (<30,000 platelets/ml of blood) due to the production of autoantibodies against the platelet cells. Bruising, nose or mouth bleeding, abnormally heavy menstruation, petechiae are some of the symptoms associated with ITP.
The disorder is known to affect 5-6 per 100,000 persons in the US, annually, with women at 2 to 3 fold higher risk for developing the disease. ITP is often an acute condition in children, and is usually followed by a viral infection. Administration of corticosteroids such as prednisone is one of the effective first-line therapies indicated for ITP. Immunosuppressants, high-dose gamma globulin injections, anti-RhD therapy and splenectomy are some of the other treatment options available for patients who do not respond to the initial treatment. The approval of Nplate offers another promising therapeutic option for chronic thrombocytopenic purpura patients not responding to earlier treatments. However, it is crucial that the patients should be closely monitored for any adverse reactions during treatment.
About Amgen Inc.: Headquartered in Thousand Oaks, California, Amgen is a biotechnology pioneer involved in developing, manufacturing and marketing innovative therapeutics against cancer, rheumatoid arthritis, kidney disease, and other serious disorders using advanced recombinant DNA and molecular biology techniques.
References
1. FDA Approves Nplate(TM) for Long-Term Treatment of Adult Chronic ITP. Press Release. Amgen Inc. Last accessed August 26, 2008.
2. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403.
3. Newland A. Emerging strategies to treat chronic immune thrombocytopenic purpura. Eur J Haematol Suppl. 2008 Feb;(69):27-33.
