2 The technology

2 The technology

2.1 Ledipasvir–sofosbuvir prevents hepatitis C virus (HCV) replication by inhibiting non‑structural protein (NS) 5A (targeted by ledipasvir) and NS5B (targeted by sofosbuvir) proteins. Ledipasvir‑sofosbuvir (Harvoni, Gilead Sciences) has a marketing authorisation in the UK for treating chronic hepatitis C in adults. However, the marketing authorisation recommends specific treatment durations for HCV genotypes 1, 3 and 4 only, and states that ledipasvir–sofosbuvir should not be used in people with HCV genotypes 2, 5 and 6. The recommended dose is 1 daily tablet containing a fixed‑dose combination of 90 mg ledipasvir and 400 mg sofosbuvir. It is taken orally for 8, 12 or 24 weeks, with or without ribavirin. The recommended treatment duration and whether ribavirin is co‑administered depends on genotype, treatment history and presence of cirrhosis. For full details of the recommended treatment durations with or without ribavirin, see table 1 of the summary of product characteristics.

2.2 The summary of product characteristics lists the following 'very common' adverse reactions for ledipasvir–sofosbuvir, with or without ribavirin: fatigue and headache. For full details of adverse reactions and contraindications, see the summary of product characteristics.

2.3 The cost of ledipasvir–sofosbuvir is £12,993.33 per 28‑tablet pack (excluding VAT; company's evidence submission). The cost of a 8‑week course of treatment is £25,986.66 and a 12‑week course is £38,979.99 (both excluding VAT), not including the cost for ribavirin. The company has agreed a nationally available price reduction for ledipasvir–sofosbuvir with the Commercial Medicines Unit. However, this contract agreement was not presented by the company and therefore it could not be considered in this appraisal. Costs may vary in different settings because of negotiated procurement discounts.

  • National Institute for Health and Care Excellence (NICE)