Hepatitis C is a virus that infects the liver. It is spread by contact with infected blood, for instance by using contaminated needles for injecting drugs or sharing razors or toothbrushes. The virus can cause inflammation of, and damage to the liver, preventing it from working properly.

Figures from 2012 suggest that around 160,000 people are chronically infected with the hepatitis C virus in England. More than half of people with chronic hepatitis C do not know they are infected because they only have mild symptoms or no symptoms at all for a long period of time. About 1 in 3 people infected with the hepatitis C virus will eventually develop liver cirrhosis, where normal liver tissue is replaced by scar tissue. A small percentage of people with chronic hepatitis C and cirrhosis also develop liver cancer.

The aims of treatment are to clear the virus from the blood to prevent progression of liver disease, and to prevent the transmission of the hepatitis C virus.

The marketing authorisation for ledipasvir-sofosbuvir recommends treatment for genotypes 1, 3 (in combination with ribavirin) and 4 hepatitis C. Genotypes 1 and 3 hepatitis C account for the majority of chronic hepatitis C cases in England (46% and 43% respectively). Genotype 4 hepatitis C accounts for around 4% of cases.

Ledipasvir-sofosbuvir is administered orally as a single tablet (with or without ribavirin) and works by inhibiting the replication of the hepatitis C virus.

Commenting on the draft guidance Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation, said: “The current mainstay of treatment for hepatitis C is interferon-based therapy. This often has to be given over a long period of time and is associated with significant side effects that increase the risk that some people may choose to discontinue treatment, or not seek it in the first place.

“Ledipasvir- sofosbuvir offers the possibility of a shortened course of treatment – in some cases as little as 8 weeks – without the need for combination therapy with interferon. This could make it more likely that people will seek treatment for their condition. In turn this could have important benefits, not just for people with chronic hepatitis, but also in reducing transmission of the virus to people without the infection. The Committee therefore acknowledged that ledipasvir-sofosbuvir is a valuable new therapy for treating chronic hepatitis C.”

The Committee also considered ledipasvir-sofosbuvir in combination with ribavirin  for people with genotype 3 chronic hepatitis C. Based on the evidence presented the Committee concluded that this could not be considered a cost-effective use of NHS resources.

Stakeholders are now able to comment on the draft recommendations which are available for public consultation. Comments received during this consultation will be fully considered by the Committee at the next meeting, and following this meeting the next draft guidance will be issued. The closing date for comments on the draft guidance is 23 March 2015.

This is draft guidance; NICE has not yet issued final guidance to the NHS. Until then, NHS bodies should make decisions locally on the funding of specific treatments.

Ends

For further information, please contact the NICE press office on 0300 323 0142 / pressoffice@nice.org.uk or out of hours on 07775 583 813.

Notes to Editors

About the draft guidance

1. The draft guidance on ledipasvir-sofosbuvir is available from the NICE website (from 00:01 on 3 March 2015). Consultation on the draft guidance closes on 23 March 2015.
2. The draft guidance states that:

Ledipasvir-sofosbuvir is recommended as an option for treating chronic hepatitis C in adults, as specified in table 1.

Table 1 Ledipasvir-sofosbuvir for treating adults with chronic hepatitis C

About ledipasvir-sofosbuvir

1. Ledipasvir-sofosbuvir (Harvoni, Gilead Sciences) prevents hepatitis C virus replication by inhibiting the NS5A (targeted by ledipasvir) and NS5B (targeted by sofosbuvir) proteins.
2. Ledipasvir-sofosbuvir has a marketing authorisation in the UK for treating chronic hepatitis C in adults. However, the marketing authorisation recommends specific treatment regimens 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.
3. The recommended dose is 1 daily tablet containing 90 mg ledipasvir and 400 mg sofosbuvir. It is taken orally as a fixed-dose combination tablet 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 for ledipasvir-sofosbuvir with or without ribavirin, see table 1 of its summary of product characteristics.
4. Ledipasvir-sofosbuvir costs £12,993.33 per 28 tablet pack (excluding VAT; company’s evidence submission). The cost of a 12 week course of treatment is £38,979.99 and a 24 week course is £77,959.98 (both excluding VAT), not including the cost for ribavirin. Costs may vary in different settings because of negotiated procurement discounts.

Summary of Appraisal Committee’s key conclusions on cost effectiveness

Treatment-naive genotype 1 HCV without cirrhosis

Incremental ICERs for 8 weeks and 12 weeks of ledipasvir–sofosbuvir in people with treatment-naive, genotype 1 HCV without cirrhosis were £9000 (compared with peginterferon alfa plus ribavirin) and £23,000 (compared with simeprevir plus peginterferon alfa and ribavirin) per QALY gained respectively.

 Treatment-naive genotype 4 HCV without cirrhosis

The Committee agreed that it would consider the ICERs presented for people with genotype 4 HCV that used data from people with genotype 1 HCV.

 Treatment-naive genotype 1 or 4 HCV with cirrhosis

Incremental ICERs for ledipasvir–sofosbuvir in people with treatment-naive genotype 1 or 4 HCV with cirrhosis were £5000 (12 weeks of treatment, compared with no treatment) and £45,000 (24 weeks of treatment, compared with sofosbuvir plus peginterferon alfa and ribavirin) per QALY gained.

 Treatment-experienced genotype 1 or 4 HCV without cirrhosis

Incremental ICERs for ledipasvir–sofosbuvir in people with treatment-experienced genotype 1 or 4 HCV without cirrhosis were £17,000 (12 weeks of treatment, compared with no treatment) and £77,500 (24 weeks of treatment, compared with simeprevir plus peginterferon alfa and ribavirin) per QALY gained.

 Treatment-experienced genotype 1 or 4 HCV with cirrhosis

ICER for 24 weeks of ledipasvir–sofosbuvir in people with treatment-experienced genotype 1 or 4 HCV with cirrhosis was £32,500 per QALY gained (compared with sofosbuvir plus peginterferon alfa and ribavirin).

 Genotype 3 HCV

The Committee noted that all the ICERs presented for those with treatment-naive genotype 3 HCV with or without cirrhosis were over £30,000 per QALY gained. It noted that the ICERs for people with treatment-experienced, genotype 3 HCV and cirrhosis for whom interferon was not suitable ranged from £18,000 to £30,500 per QALY gained for 24 weeks of ledipasvir–sofosbuvir plus ribavirin (compared with no treatment), and agreed this may increase when accounting for the additional uncertainty associated with the evidence.

About chronic hepatitis C

1. There are 6 major genotypes and several subtypes of the hepatitis C virus, the prevalence of each vary geographically.
2. Genotypes 1 and 3 account for the majority of chronic hepatitis C cases in England (46% and 43% respectively).
3. People with genotype 2 hepatitis C generally respond to treatment better than those with genotype 1, 3, 4, 5 or 6.
4. For people with mild disease, a ‘watchful waiting’ approach may be agreed, on an individual basis, between the patient and clinician.
5. Although 15 to 20% of people infected with the hepatitis C virus naturally clear their infections within 6 months, the remainder develop chronic hepatitis which can be life-long.
6. NICE Technology Appraisal guidance 331 for people with genotypes 1 and 4 chronic hepatitis C, recommends simeprevir in combination with peginterferon alfa and ribavirin as an option.
7. For people with genotypes 1 to 6 chronic hepatitis C NICE Technology Appraisal guidance 330 recommends sofosbuvir in combination with ribavirin, with or without peginterferon alfa, as an option for specific people.
8. For people with genotype 1 chronic hepatitis C NICE guidance also recommends telaprevir in combination with peginterferon alfa and ribavirin (NICE Technology Appraisal 252) or boceprevir in combination with peginterferon alfa and ribavirin (NICE Technology Appraisal 253).
9. Other NICE guidance (NICE Technology Appraisal 75 and NICE Technology Appraisal 106) recommend that standard treatment for the majority of people with chronic hepatitis C is peginterferon alfa and ribavirin combination therapy. Monotherapy with peginterferon alfa-2a or peginterferon alfa-2b is recommended for patients who are unable to tolerate ribavirin or for whom ribavirin is contraindicated.
10. Other NICE guidance on hepatitis C (NICE technology appraisal 200) also recommends that people who have been previously treated with peginterferon alfa and ribavirin or with peginterferon alfa monotherapy have an option to receive further courses of peginterferon alfa and ribavirin.
11. Shortened courses of peginterferon alfa and ribavirin are also recommended as an option for certain patient subgroups (NICE technology appraisal 200).