Thrombocytopoenia - romiplostim

Patients with idiopathic thrombocytopoenic purpura, or ITP, have a low platelet count with no obvious cause.

While thrombocytopoenia is a common side effect of cancer chemotherapy and is often associated with other diseases such as myelodysplastic syndrome, chronic liver disease and AIDS, there is not always an obvious cause, but it is probably a result of the immune system destroying platelets, or antibodies may be preventing the bone marrow from making them effectively.

Current drug treatments focus on suppressing the immune system, but this is not particularly specific, or other treatments such as administering replacement blood products. A new treatment being developed by Amgen, romiplostim, is a genetically engineered peptibody thrombopoeietic growth factor, which binds to the thrombopoeietin receptor and has been designed to reduce the chances of the body developing antibodies to it.¹

Numerous trials have been carried out. A randomised blinded placebo controlled trial was run in 48 healthy volunteers to determine its safety, tolerability, pharmacokinetics and pharmacodynamics.² Subjects were given the drug in doses between 0.3 and 10 µg/kg as a single intravenous or subcutaneous dose, or placebo. The drug raised the platelet response in a dose-dependent manner regardless of the administration route, and peak platelet counts were achieved 12 to 16 days after dosing, with the increase in platelet count initially being seen after three to five days.

An open label, dose escalating trial has also been carried out to look at its safety and efficacy and determine the preferred dose in 16 patients with ITP.³ Subjects were given doses from 30 to 500µg on days 1 and 15 - or a week later if the platelet count remained above 50 billion/litre on day 15. Two were not given the second injection because their platelet count rose to above 1,000 billion/litre. The majority of adverse events were mild to moderate, and the most common was headache. All subjects had a platelet response, and there was a median of 10 days between the first dose and the peak platelet count.

The long term safety and efficacy of escalating subcutaneous doses of romiplostim has also been studied in an extension of previous trials.⁴ Subjects received the same starting dose as the final dose in their initial trial, and those who had been given placebo started off on the lowest dose. The doses were adjusted according to the patients" response, and some patients have now been treated for more than two years. Median time to response was 3.1 weeks, and the mean dose at first response was 3.4µg/kg. At any one time, the mean percentage of patients with normal platelet counts was more than 80%.