2 The technology
2.1 Ranibizumab (Lucentis, Novartis) belongs to a class of drugs that blocks the action of vascular endothelial growth factor A (VEGF-A). In diabetic macular oedema, VEGF-A causes blood vessels to leak in the macula, the area of the retina responsible for the clearest vision. The accumulated fluid causes swelling, or oedema, which impairs vision. By inhibiting the action of VEGF-A, ranibizumab reduces oedema and limits visual loss or improves vision. Ranibizumab has a marketing authorisation for 'the treatment of visual impairment due to diabetic macular oedema in adults'.
2.2 The summary of product characteristics states that treatment should be given monthly and continued until maximum visual acuity is reached – that is, until visual acuity has been stable for 3 consecutive months. Thereafter, visual acuity should be monitored monthly. Treatment is resumed if monitoring indicates a loss of visual acuity caused by diabetic macular oedema, and continued until visual acuity has remained stable for 3 consecutive months. The interval between doses should not be shorter than 1 month.
2.3 Contraindications to ranibizumab include known hypersensitivity to the active substance or to any of its excipients, active or suspected ocular or periocular infections and active severe intraocular inflammation. Adverse reactions of treatment are mostly limited to the eye. Those commonly reported in clinical trials include vitritis, vitreous detachment, retinal haemorrhage, visual disturbance, eye pain, vitreous floaters, conjunctival haemorrhage, eye irritation, sensation of a foreign body in the eye, increased production of tears, blepharitis, dry eye, ocular hyperaemia, itching of the eye and increased intraocular pressure. Nasopharyngitis, arthralgia and headaches are also reported as common adverse reactions. For full details of adverse reactions and contraindications, see the summary of product characteristics.
2.4 Ranibizumab is administered as a single intravitreal injection of 0.5 mg. Each vial of ranibizumab contains 2.3 mg in 0.23 ml; overfilling is considered necessary to achieve an injectable dose of 0.5 mg. The list price of ranibizumab is £742.17 per vial (excluding VAT; 'British national formulary' [BNF] edition 64). Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of ranibizumab (Novartis) has agreed a patient access scheme with the Department of Health which makes ranibizumab available with a discount applied to all invoices. The size of the discount is commercial in confidence (see section 5.3). 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.