3 The technology
3.1 Denosumab (XGEVA, Amgen) is a fully human monoclonal antibody that reduces osteoclast-mediated bone destruction by inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL), which is the primary mediator of increased osteoclast activity. Denosumab has a marketing authorisation for the prevention of skeletal-related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with bone metastases from solid tumours. The recommended dose of denosumab for the prevention of skeletal-related events in bone metastases from solid tumours is 120 mg every 4 weeks. It is administered as a single subcutaneous injection into the thigh, abdomen or upper arm.
3.2 The summary of product characteristics lists the following adverse reactions for denosumab: dyspnoea, diarrhoea, osteonecrosis of the jaw, hyperhidrosis, tooth extraction, hypophosphataemia and hypocalcaemia. Denosumab is contraindicated in people with severe, untreated hypocalcaemia. For full details of adverse reactions and contraindications, see the summary of product characteristics.
3.3 The cost of a 120 mg vial is £309.86 (excluding VAT; British National Formulary [BNF] 63). A year of treatment (13 doses) would cost £4028.18 (excluding VAT). Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of denosumab has agreed a patient access scheme with the Department of Health, in which a discount on the list price of denosumab is offered. 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.