June 16, 2014

NICE consults on draft guidance on the drug sofosbuvir (Sovaldi) for treating hepatitis C

Provided by NICE (National Institute for Health and Care Excellence)

In draft recommendations published today healthcare guidance body NICE is asking Gilead Sciences for more information on its product sofosbuvir (Sovaldi), for the treatment of chronic hepatitis C.

Hepatitis C is a virus that infects the liver. It is spread by contact with infected blood, usually as a result of using contaminated needles for injecting drugs. 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 the England. More than half of people with chronic hepatitis C do not know they are infected because often, 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Commenting on the draft guidance Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation, said: “Poor diagnosis rates, combined with a high number of new infections annually means that chronic hepatitis C presents a major public health challenge.

“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.

“The availability of new treatments, like sofosbuvir, that can shorten the duration of interferon-based therapy or which in some cases don't need to be taken with interferon at all, would potentially encourage more people to seek treatment.

“The available evidence shows that sofosbuvir is an effective treatment for chronic hepatitis C in certain patients. However, evidence is lacking for some subgroups of patients with chronic hepatitis C, and there are also substantial uncertainties in the evidence base presented by the manufacturer. The Committee has therefore requested further information from the manufacturer before it can decide whether sofosbuvir is a cost-effective use of NHS resources.”

Consultees are now able to comment on the preliminary 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 4 July 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.


Notes to Editors


About the draft guidance

1. The draft guidance on is available from the NICE website. Consultation on the draft guidance closes on 4 July 2014.

2. The draft guidance states that:

1.1 The Committee is minded not to recommend sofosbuvir within its marketing authorisation for treating chronic hepatitis C in adults.

1.2 The Committee recommends that NICE requests further analyses from the manufacturer for sofosbuvir in combination with ribavirin, with or without peginterferon alfa compared with peginterferon alfa and ribavirin in people with genotype 1 and genotype 3 chronic hepatitis C, to be made available for the second Appraisal Committee meeting, as follows:

  • Revised cost-effectiveness analyses presented separately for people with and without cirrhosis, with and without HIV-co-infection, and by treatment history. The analyses should incorporate the following assumptions:
    • a transition from the sustained virological response-cirrhotic health state to the hepatocellular carcinoma health state, using the transition probability estimates from Cardoso et al. (2010)
    • alternative sustained virological response estimates for peginterferon alfa and ribavirin including those from Hadziyannis et al. (2004) (see section 4.14)
    • alternative utility increments after sustained virological response including SF-36 values from the trials collected at 24 weeks post-treatment, and Vera-Llonch et al. (2013) (see section 4.18)
    • alternative costs for ribavirin in the model (see section 4.15)
  • Sensitivity analyses that include the above mentioned assumptions and also explore the effect on the incremental cost-effectiveness ratios (ICERs) of the following:
    • assuming that up to 100% of people with genotype 3 HCV receive sofosbuvir plus ribavirin for 24 weeks (see section 4.16)
    • assuming an increased proportion of interferon-eligible people may be unwilling to have interferon treatment and therefore receive sofosbuvir plus ribavirin for 24 weeks (see section 4.17)
    • allowing people aged 35 and 55 years to enter the model (see section 4.12)
    • variation in all-cause mortality by assuming the population entering the model comprises 61% men and 39% women, in line with estimates from Wright et al. (2006) (see section 4.12).
  • For all the above analyses:
    • report probabilistic ICERs
    • use a discount rate of 3.5% for costs and benefits in line with the NICE reference case
    • provide a revised fully executable economic model to check the above revisions.
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 average duration of treatment is 12 or 24 weeks depending on the patient's hepatitis C virus genotype and history of prior treatment with interferon.

4. Sofosbuvir combination treatment regimens without peginterferon alfa for patients with genotype 1, 4, 5 and 6 hepatitis C virus infection have not been investigated in phase 3 studies. According to the summary of product characteristics for sofosbuvir, treatment regimens without peginterferon alfa should only be used for patients with genotype 1, 4, 5 and 6 hepatitis C virus infection if they are intolerant to or ineligible for peginterferon alfa therapy and are in urgent need of treatment.

5. The summary of product characteristics for sofosbuvir also states that for all genotypes, consideration should be given to potentially extending the duration of therapy from 12 weeks up to 24 weeks especially for subgroups of people who have one or more factors historically associated with lower response rates to interferon-based therapies (such as people with advanced liver fibrosis or cirrhosis, high baseline viral concentrations, prior unresponsiveness to peginterferon alfa and ribavirin combination therapy, or a non-CC nucleotide polymorphism near their IL28B gene [that is, people without the CC genotype IL28B polymorphism]; or for people of African and Caribbean family origin).

6. 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.

7. In April 2014 NHS England issued an interim clinical commissioning policy stating that it would commission sofosbuvir in combination with daclatasvir or ledipasvir with or without ribavirin for patients who meet specific criteria and are considered to be at significant risk of death or irreversible damage within the next 12 months, irrespective of genotype. The combination of sofosbuvir and daclatasvir or ledipasvir with or without ribavirin is not being considered in this ongoing appraisal.

About NICE

The National Institute for Health and Care Excellence (NICE) is the independent body responsible for driving improvement and excellence in the health and social care system. We develop guidance, standards and information on high-quality health and social care. We also advise on ways to promote healthy living and prevent ill health.

Formerly the National Institute for Health and Clinical Excellence, our name changed on 1 April 2013 to reflect our new and additional responsibility to develop guidance and set quality standards for social care, as outlined in the Health and Social Care Act (2012).

Our aim is to help practitioners deliver the best possible care and give people the most effective treatments, which are based on the most up-to-date evidence and provide value for money, in order to reduce inequalities and variation.

Our products and resources are produced for the NHS, local authorities, care providers, charities, and anyone who has a responsibility for commissioning or providing healthcare, public health or social care services.

To find out more about what we do, visit our website: www.nice.org.uk and follow us on Twitter: @NICEComms.

This page was last updated: 16 June 2014


No comments:

Post a Comment