Nplate - romiplostim

What is Nplate?

Nplate is a powder for preparing a solution for injection. It contains the active ingredient romiplostim.

What is Nplate used for?

Nplate is used in adults with chronic immune thrombocytopenic purpura (PTI), a disease in which the patient's immune system destroys platelets (components of blood that contribute to clotting). Patients with ITP have low platelet counts and are at risk of bleeding.

Nplate is used in patients who have already been treated with medicines such as corticosteroids or immunoglobulins and where the spleen has been removed, if these treatments have not worked. The use of the medicine can also be considered in patients who have been on PTI therapy, have a spleen and cannot undergo surgery. The spleen is an organ that participates in the destruction of platelets.

Because the number of patients with ITP is low, the disease is considered 'rare', and Nplate was designated an 'orphan medicine' (a medicine used for rare diseases) on 27 May 2005.

The medicine can only be obtained with a prescription.

How is Nplate used?

Treatment with Nplate should be supervised by a doctor experienced in treating blood disorders.

Nplate is given once a week with an injection under the skin. The initial dose depends on the patient's weight and is then adjusted each week to keep the platelet count at the desired levels. Treatment can be interrupted if the platelets reach too high levels.

Nplate therapy should be discontinued after four weeks of treatment at the maximum dose if the platelet count does not reach levels high enough to reduce the risk of bleeding. Nplate should be used with caution in patients who have liver or kidney problems since it has not been formally studied in this group.

How does Nplate work?

The active substance in Nplate, romiplostim, is a medicine that stimulates platelet production. In the body, a hormone called 'thrombopoietin' stimulates the production of platelets in the bone marrow. Romiplostim is a protein created (specifically designed) so that it can bind to

thrombopoietin receptors and stimulate them. Emulating the action of thrombopoietin, romiplostim stimulates the production of platelets, increasing the blood platelet count.

Romiplostim is produced by a method called 'recombinant DNA technology': it is produced by a bacterium that has received a gene (DNA) which makes it capable of producing romiplostim.

What studies have been carried out on Nplate?

The effects of Nplate were first tested in experimental models before being studied in humans.

Nplate was compared with placebo (a dummy treatment) in two main studies involving adults with chronic ITP. The first study included 63 patients already subjected to removal of the spleen but where the disease was not yet controlled. The second study included 62 patients who still had the spleen and who had been on ITP therapy in the past.

In both studies, the main measure of effectiveness was the number of patients who had a lasting response to treatment, ie a platelet count of more than 50 million per milliliter for at least six of the last eight weeks of the 24-week treatment period, without the need for other PTI medicines. A platelet count below 30 million per milliliter puts ITP patients at risk of bleeding, while a normal level is between 150 and 400 million per milliliter.

What benefit has Nplate shown during the studies?

Nplate was more effective than placebo in increasing blood platelet counts. In the study of patients whose spleen was removed, 38% of patients had a lasting response to treatment with Nplate (16 of 42), compared to none of the 21 patients receiving placebo. In the study of patients with spleen, 61% of patients had a lasting response to treatment with Nplate (25 out of 41), compared with 5% of patients receiving placebo (1 of 21).

What is the risk associated with Nplate?

The most common side effect with Nplate (seen in more than 1 patient in 10) is headache. For the full list of all side effects reported with Nplate, see the Package Leaflet.

Nplate should not be used in people who may be hypersensitive (allergic) to romiplostim, to any of the other substances or to the proteins produced by Escherichia coli (a bacterium).

Why has Nplate been approved?

The Committee for Medicinal Products for Human Use (CHMP) noted that the efficacy of Nplate was demonstrated both in patients who had their spleen removed and those who still had the spleen. However, since the removal of the spleen is a potential cure for ITP, the committee decided that Nplate should only be used in patients with the spleen if they cannot be subjected to surgery. Therefore, the CHMP decided that Nplate's benefits are greater than its risks in adult splenectomised patients with chronic immune-thrombocytopenic (idiopathic) purpura who are refractory to other treatments and can be considered as a second-line treatment for non-splenectomized adult patients in which surgery is contraindicated. The committee recommended the granting of a marketing authorization for Nplate.

What measures are being taken to ensure the safe use of Nplate?

The company that produces Nplate will supply information kits to doctors in each Member State. The kits will include information on the safety and efficacy of Nplate and notes to remind doctors of how to use the medicine and the need to discuss the benefits and risks of Nplate with patients. The doctors will also receive a 'calculator for the dose' which will help them calculate the volumes of Nplate to be injected. These volumes can sometimes be very small.