2 The technology
2.1 Lumacaftor–ivacaftor (Orkambi, Vertex Pharmaceuticals) is a systemic protein modulator. Lumacaftor is a corrector of the cystic fibrosis transmembrane conductance regulator (CFTR) and ivacaftor is a potentiator of the CFTR. Lumacaftor–ivacaftor has a marketing authorisation in the UK for treating cystic fibrosis in people 12 years and older who are homozygous for the F508del mutation (that is, have 2 copies of the mutation) in the CFTR gene. The recommended dose is 2 tablets (each tablet contains 200 mg lumacaftor and 125 mg ivacaftor) taken orally every 12 hours (a total daily dose of 800 mg lumacaftor and 500 mg ivacaftor).
2.2 The summary of product characteristics lists the following very common adverse reactions for lumacaftor–ivacaftor: abdominal pain, bacteria in sputum, diarrhoea, dizziness, dyspnoea, headache, nasal congestion, nasopharyngitis and nausea. For full details of adverse reactions and contraindications, see the summary of product characteristics.
2.3 The cost of lumacaftor–ivacaftor is £8,000 per 112‑tablet pack (excluding VAT; company's evidence submission). The cost of a 1‑year course of treatment is £104,000 (excluding VAT). Costs may vary in different settings because of negotiated procurement discounts.