15 August 2014

NICE consults on further draft guidance on the drug sofosbuvir (Sovaldi) for treating hepatitis C

In further draft guidance NICE has recommended sofosbuvir (Sovaldi, Gilead Sciences) as a treatment option for some people with chronic hepatitis C. The positive recommendation follows receipt of additional information about the drug’s cost effectiveness from the manufacturer.

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.

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.

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. Sofosbuvir is an oral antiviral drug used to prevent hepatitis C viral replication in infected cells.

Commenting on the draft guidance Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation, said: “Hepatitis C is a major public health challenge. It is difficult to diagnose and each year there are many new infections.

“The problem is made worse because the potential side-effects of current treatments, such as interferon, which often needs to be given for a long period of time, mean that many people with the disease either don’t complete the full course, or are reluctant to seek treatment in the first place.

“New treatments, like sofosbuvir, can shorten the duration of interferon-based therapy and in some cases don’t need to be taken with interferon at all. This could potentially encourage more people to seek treatment.

“Our previous draft guidance concluded that the available evidence showed sofosbuvir to be an effective treatment for chronic hepatitis C in certain patients. However, there were some uncertainties in the evidence base for some subgroups of patients with chronic hepatitis C. The Committee has considered the additional evidence it requested from the manufacturer and we are pleased to be able to provisionally recommend sofosbuvir as a clinically and cost effective treatment for some people with chronic hepatitis C.”

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 5 September 2014.

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

Notes to Editors

About the draft guidance

  1. The draft guidance states that:

Sofosbuvir in combination with peginterferon alfa and ribavirin

 1.1      Sofosbuvir, in combination with peginterferon alfa and ribavirin, is recommended as an option for treating genotype 1 chronic hepatitis C in adults.

1.2       Sofosbuvir, in combination with peginterferon and ribavirin, is recommended as an option for treating genotype 3 chronic hepatitis C in adults with cirrhosis.

1.3       Sofosbuvir, in combination with peginterferon alfa and ribavirin, is recommended as an option for treating genotype 3 chronic hepatitis C in adults without cirrhosis, only if they had treatment for hepatitis C before.

1.4       Sofosbuvir, in combination with peginterferon alfa and ribavirin, is not recommended for treating genotype 4, 5 and 6 chronic hepatitis C in adults.

 

Sofosbuvir in combination with ribavirin alone

1.5       Sofosbuvir, in combination with ribavirin alone is not recommended for treating adults with genotype 1, 4, 5 and 6 chronic hepatitis C.

1.6       Sofosbuvir, in combination with ribavirin, is recommended as an option for treating genotype 2 chronic hepatitis C in adults only if they:

  • have not had treatment for chronic hepatitis C before and are intolerant to or ineligible for interferon therapy or
  • have had treatment for chronic hepatitis C before, regardless of interferon eligibility.

1.7       Sofosbuvir, in combination with ribavirin, is recommended as an option for treating genotype 3 chronic hepatitis C only in adults with cirrhosis.

1.8       People currently receiving treatment initiated within the NHS with sofosbuvir that is not recommended for them by NICE in this guidance should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

 

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. Current NICE guidance (NICE technology appraisal 75 and NICE technology appraisal 106) recommends 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.
  6. 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.
  7. Shortened courses of peginterferon alfa and ribavirin are also recommended as an option for certain patient subgroups (NICE technology appraisal 200).
  8. For people with genotype 1 chronic hepatitis C, who have not been previously treated or who have been previously treated, 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).

 

About sofosbuvir

  1. Sofosbuvir (Sovaldi, Gilead Sciences) is an antiviral drug used to prevent hepatitis C viral replication in infected cells. It is administered orally.
  2. Sofosbuvir has a UK marketing authorisation for use ‘in combination with other medicinal products for treating chronic hepatitis C in adults’. The recommended dose is one 400mg tablet daily. The summary of product characteristics for sofosbuvir states that peginterferon alfa and ribavirin, or ribavirin only, are the recommended co-administered medicinal products for use with sofosbuvir.
  3. The duration of treatment is 12 or 24 weeks depending on the patient’s hepatitis C virus genotype and history of prior treatment with interferon.
    1. The cost of sofosbuvir is £11,660.98 per 28-tablet pack of 400 mg tablets (excluding VAT, ‘British national formulary’ [BNF] May 2014). The cost of a 12-week course of treatment is £34,982.94 and a 24-week course is £69,965.88 (both excluding VAT), not including the cost for ribavirin and peginterferon alfa. Costs may vary in different settings because of negotiated procurement discounts.

Summary of Appraisal Committee’s key conclusions on cost effectiveness

Genotype 1

  1. The ICER for treatment with sofosbuvir plus peginterferon and ribavirin compared with peginterferon and ribavirin was £17,500 per QALY gained in treatment naïve patients.
  2. The Committee also considered sofosbuvir plus peginterferon and ribavirin to be cost effective compared with boceprevir plus peginterferon and ribavirin, and telaprevir in combination with peginterferon and ribavirin (ICERS of approximately £10,300 and £15,400 per QALY gained respectively).
  3. The Committee considered sofosbuvir plus peginterferon and ribavirin to be cost effective in treatment experienced patients compared with peginterferon and ribavirin, boceprevir and ribavirin and telaprevir and ribavirin with ICERs of approximately £12,600, £700 and £8200 per QALY gained respectively.
  4. Sofosbuvir plus ribavirin was not recommended in people for whom interferon was unsuitable (regardless of previous treatment) because of the higher ICER compared with standard care (no treatment) which was in excess of £47,500 per QALY gained in the combined cirrhotic and non-cirrhotic cohort.


Genotype 2

  1. Sofosbuvir plus ribavirin compared with peginterferon and ribavirin in people who were treatment experienced had an ICER of £12,500 per QALY gained. However, in the treatment naïve group the treatment was not recommended because of the high ICER of £46,300 per QALY gained.
  2. The Committee considered sofosbuvir plus ribavirin to be clinically effective and cost effective compared with no treatment in people for whom treatment with interferon was unsuitable regardless of treatment experience (with ICERs of approximately £12,500 and £8500 per QALY gained respectively).


Genotype 3

  1. The Committee considered the extended treatment duration (24 weeks) of sofosbuvir plus with ribavirin to be clinically effective compared with peginterferon alfa and ribavirin. The Committee considered sofosbuvir plus peginterferon alfa and ribavirin to be cost effective in people who were treatment naive with cirrhosis (with an ICER of approximately £6600 per QALY gained) but not in people who were treatment naive without cirrhosis (with a high ICER of approximately £40,600 per QALY gained). Treatment was recommended in treatment-experienced patients regardless or cirrhotic status with ICERs of below approximately £19,000 per QALY gained
  2. The Committee considered the cost effectiveness of sofosbuvir plus ribavirin to be acceptable in people who were not eligible for peginterferon alfa regardless of previous treatment in people who had cirrhosis with ICERs of approximately £10,500 per QALY gained in treatment naive and £19,200 per QALY gained treatment experienced patients. The Committee did not consider sofosbuvir in combination with ribavirin to be cost effective in non-cirrhotic patients with ICERs of approximately £28,000 and £31,400 per QALY gained in treatment-naive and experienced patients respectively.


Genotypes 4, 5 and 6

 The Committee considered sofosbuvir in combination with ribavirin with or without peginterferon alpha to be clinically effective compared with peginterferon and ribavirin in people with treatment naïve and experienced HCV genotypes 4, 5 and 6.

13. The Committee did not consider sofosbuvir in combination with peginterferon alpha and ribavirin in people who were eligible for interferon to be cost effective in the treatment naive or experienced populations given the high degree of uncertainty in ICERs in excess of approximately £26,800 per QALY gained. In addition the Committee did not consider sofosbuvir plus ribavirin in people who were not eligible for interferon to be cost effective given the high degree of uncertainty in ICERs of approximately £26,800 per QALY gained. 

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We are pleased to be able to provisionally recommend sofosbuvir as a clinically and cost effective treatment for some people with chronic hepatitis C

Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation