3 The technology
3.1 Eculizumab (Soliris, Alexion Pharma UK) is a human monoclonal antibody that binds to complement C5 and blocks prothrombotic and pro‑inflammatory processes. It is produced from murine myeloma cells by recombinant DNA technology. Eculizumab has a marketing authorisation in the UK 'in adults and children for the treatment of patients with atypical haemolytic uraemic syndrome (aHUS)'. It is also licensed for use in people with paroxysmal nocturnal haemoglobinuria.
3.2 Eculizumab is currently commissioned, through an interim commissioning policy, by NHS England in line with the Clinical Commissioning Policy Statement: Eculizumab for atypical haemolytic uraemic syndrome for:
new patients with aHUS (defined to include those with a functioning kidney), and
existing patients who are on dialysis and are suitable for a kidney transplant.
The policy is currently administered through an interim national aHUS service at the Newcastle Upon Tyne Hospitals NHS Foundation Trust. An evidence submission from NHS England was provided to the Committee, which described the policy in detail.
3.3 In adults and adolescents (people aged 12–17 years), the most common adverse reactions with eculizumab are headache and leukopenia. The most common adverse reactions in paediatric patients (children aged 2 months to 11 years) are diarrhoea, vomiting, pyrexia, upper respiratory tract infection and headache. Eculizumab use is associated with an increased risk of meningococcal infection. All patients are vaccinated against meningococcal infection before starting treatment with eculizumab and are revaccinated in accordance with guidelines. Patients are informed of the signs and symptoms of meningococcal infection and are provided with a safety card. For full details of adverse reactions and contraindications, see the summary of product characteristics and the European public assessment report.
3.4 Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12–16 days. The summary of product characteristics for eculizumab states that 'treatment is recommended to continue for a patient's lifetime, unless discontinuation of treatment is clinically indicated'. Patients under 18 years with a body weight of 40 kg or more are treated in line with the adult dosing recommendations. Paediatric patients with a body weight below 40 kg have their dose adjusted by body weight. Eculizumab costs £3150 per 30 ml (10 mg/ml) vial (excluding VAT; British national formulary, online July 2014). The total cost of eculizumab per adult is estimated to be about £340,200 (initial and maintenance treatment) in the first year of treatment and about £327,600 for 1 year of treatment on the recommended maintenance dose.