2 The technology
2.1 Romiplostim (Nplate, Amgen) is a protein that mimics the action of thrombopoietin by acting as an agonist at thrombopoietin receptors. It stimulates the differentiation and proliferation of bone marrow cells responsible for producing platelets (megakaryocytes), thereby increasing platelet production and platelet counts (concentrations). Immune (idiopathic) thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterised by increased platelet destruction and, in some cases, inadequate platelet production. The disorder can result in low platelet counts and bleeding. Chronic ITP is defined as that which lasts longer than 12 months. Clinicians in the UK treat people with ITP as needed with 'rescue therapies' (corticosteroids, intravenous immunoglobulins and platelet infusions) and thereafter, as needed, with 'active treatments' (rituximab, immunosuppressive agents including azathioprine, mycophenolate mofetil and ciclosporin, danazol, dapsone, and cytotoxic agents including cyclophosphamide and vinca alkaloids). Romiplostim has a marketing authorisation 'for chronic immune (idiopathic) thrombocytopenic purpura (ITP) patients 1 year of age and older who are refractory to other treatments (e.g. corticosteroids, immunoglobulins)'.
2.2 The summary of product characteristics (SPC) states that the recommended initial dose of romiplostim is 1 microgram/kg of actual body weight, administered once weekly as a subcutaneous injection. The dose may be increased by increments of 1 microgram/kg until a platelet count equal to or above 50 × 109 platelets per litre of blood is reached. A maximum dose of 10 micrograms/kg once weekly should not be exceeded. Platelet counts should be measured weekly until a stable count equal to or above 50 × 109 platelets per litre is observed for at least 4 weeks without adjusting the dose. Thereafter, platelet counts should be measured monthly. Treatment with romiplostim should be stopped if the platelet count does not increase sufficiently to avoid clinically significant bleeding after 4 weeks of romiplostim therapy at the highest weekly dose of 10 micrograms/kg. Romiplostim should also be stopped if a peripheral blood smear indicates increased bone marrow reticulin as well as if a loss of efficacy is observed. For full details of dose and administration, see the SPC.
2.3 The SPC lists special warnings and precautions for the use of romiplostim, including: recurrence of thrombocytopenia and bleeding after stopping treatment; increased bone marrow reticulin; thrombotic and/or thromboembolic complications (described by the SPC as a 'theoretical risk' from platelet counts above the reference range); and loss of response (which could result from immunogenicity or increased bone marrow reticulin). The SPC lists headache as a 'very common' undesirable effect. For full details of side effects and contraindications, see the SPC.
2.4 The SPC states that romiplostim is supplied in both 500 microgram and 250 microgram vials. However, only 250 microgram vials are available in the UK. Romiplostim costs £1.93 per microgram, so a 250 microgram vial costs £482 (excluding VAT; 'British national formulary' [BNF] edition 60). The cost of treatment varies depending on the patient's weight and the dosing regimen. The cost will also be affected by any waste that results from discarding any unused drug from the single use of a 250 microgram vial. The SPC states that romiplostim is a sterile but unpreserved product and therefore is intended for single use only. The annual cost of romiplostim treatment for a person weighing 80 kg would be £8020 at a dose of 1 microgram/kg weekly and £80,204 at a dose of 10 micrograms/kg weekly (assuming no waste). The manufacturer of romiplostim (Amgen) has agreed a patient access scheme with the Department of Health which makes romiplostim available with a discount on the 250 microgram vial. The size of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. The manufacturer has agreed that the patient access scheme will remain in place until any review of this NICE technology appraisal guidance is published.