NICE guidance recommends sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen) for treating hepatitis C

Healthcare guidance body NICE has today published final guidance recommending sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen) as treatment options for some people with chronic hepatitis C.

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.

About a third of people infected with the hepatitis C virus will eventually develop liver cirrhosis, where normal liver tissue is replaced by scar tissue. A small number of people with chronic hepatitis C and cirrhosis also go on to 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 and simeprevir are oral antiviral drugs used to prevent hepatitis C viral replication in infected cells.

Sofosbuvir has a marketing authorisation in the UK for use in combination with other medicinal products for treating chronic hepatitis C in adults. The guidance on sofosbuvir recommends its use in combination with ribavirin, with or without peginterferon alfa, as an option for some people with genotypes 1- 6 chronic hepatitis C.[1]

Simprevir has a marketing authorisation in the UK for use in combination with other medicinal products for treating adults with genotype 1 or 4 chronic hepatitis C. The guidance on simeprevir recommends its use, in combination with peginterferon alfa and ribavirin, as an option for treating both genotypes 1 and 4 chronic hepatitis C in adults.

More data on the use of simeprevir in combination with sofosbuvir to treat chronic hepatitis C in people who can’t tolerate or aren’t eligible for treatment with interferon is due to become available soon. Therefore recommendations on this treatment combination will now be developed in separate guidance.

Commenting on today’s guidance Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation, said: “Poor diagnosis rates - estimates suggest around 50% of people with the condition in England remain undiagnosed - combined with a high number of new infections annually make hepatitis C a major public health challenge. But even when people are diagnosed, the long duration and potentially unpleasant side-effects of current interferon-based treatments can discourage people with the disease from completing the full course, or even from seeking treatment in the first place.

“New treatments, like sofosbuvir and simeprevir, can shorten the length of interferon-based therapy and in some situations don’t need to be taken with interferon at all. Both drugs can also be given to people who have previously been treated but did not clear the virus, in people whose condition has relapsed, or in people who have become re-infected after treatment.

“Sofosbuvir and simeprevir could therefore be valuable treatment options for people with chronic hepatitis C. This is good news, not just for people with chronic hepatitis C, but also because having more effective treatments for the condition could reduce the spread of the virus.”

 

Following a request from NHS England and consultation with stakeholders, the period during which NHS England has to comply with the recommendations for sofosbuvir is extended to 31 July 2015. The period during which NHS England has to comply with the recommendations for simeprevir has not been extended.

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About the guidance on sofosbuvir

1. The guidance on sofosbuvir is available from the NICE website (from 00:01 on 25 February 2015).
2. The guidance states that:

1.1  Sofosbuvir is recommended as an option for treating chronic hepatitis C in adults, as specified in table 1.

1.2  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.

Table 1 Sofosbuvir for treating adults with chronic hepatitis C

	Sofosbuvir in combination with peginterferon alfa and ribavirin		Sofosbuvir in combination with ribavirin
Genotype	Treatment history	Recommendation	Treatment history	Recommendation
Adults with genotype 1 HCV	All	Recommended	All	Not recommended
Adults with genotype 2 HCV	All	Not licensed for this population	Treatment- naive	Only recommended for people who are intolerant to or ineligible for interferon
			Treatment- experienced	Recommended
Adults with genotype 3 HCV	Treatment-naive	Only recommended for people with cirrhosis	Treatment-naive	Only recommended for people with cirrhosis who are intolerant to or ineligible for interferon
	Treatment-experienced	Recommended	Treatment-experienced	Only recommended for people with cirrhosis who are intolerant to or ineligible for interferon
Adults with genotype 4, 5, or 6 HCV	All	Only recommended for people with cirrhosis	All	Not recommended
HCV – hepatitis C virus Treatment-naive – the person has not had treatment for chronic hepatitis C Treatment-experienced – the person’s hepatitis C has not adequately responded to interferon-based treatment

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.
4. 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 plus peginterferon and ribavirin, and telaprevir plus peginterferon 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 population of people with and without cirrhosis .

Genotype 2

1. The ICER for sofosbuvir plus ribavirin compared with peginterferon and ribavirin in people who were treatment experienced was £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 £8200 and £8600 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 with treatment-naive HCV with cirrhosis (with an ICER of approximately £6600 per QALY gained) but not in people with treatment-naive HCV without cirrhosis (with a high ICER of approximately £40,600 per QALY gained). Treatment was recommended in people with treatment-experienced HCV regardless or cirrhosis 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 with cirrhosis who were not eligible for peginterferon alfa regardless of previous treatment with ICERs of approximately £10,500 per QALY gained for treatment-naive HCV and £19,200 per QALY gained for treatment-experienced HCV. The Committee did not consider sofosbuvir in combination with ribavirin to be cost effective in people without cirrhosis with ICERs of approximately £28,000 and £31,400 per QALY gained in treatment-naive and experienced HCV 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.

1. The Committee noted that the ICER for sofosbuvir plus peginterferon alfa and ribavirin compared with peginterferon and ribavirin in the combined cohort of people with treatment naive genotype 4, 5 and 6 HCV was £39,100 per QALY gained. The Committee did not consider sofosbuvir plus peginterferon alfa and ribavirin to be cost effective in people with genotype 4, 5 or 6 HCV without cirrhosis. The Committee considered that ICERs in the population with cirrhosis are consistently lower than in people without cirrhosis and that considering the high unmet need in the population of people with genotype 4, 5 and 6 with cirrhosis, the Committee could consider sofosbuvir plus peginterferon alpha and ribavirin to be cost effective in the treatment naive or experienced populations with ICERs that could be between £20,000 and £30,000 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. 

About the guidance on simeprevir

1. The guidance on simeprevir is available from the NICE website (from 00:01 on 25 February 2015).
2. The guidance states that:
   
   1.1  Simeprevir, in combination with peginterferon alfa and ribavirin, is recommended within its marketing authorisation as an option for treating genotype 1 and 4 chronic hepatitis C in adults.
3. As part of this appraisal the Committee originally considered the effectiveness of simeprevir in combination with sofosbuvir. In the appraisal consultation document the Committee concluded that the true magnitude of the effect of simeprevir in combination with sofosbuvir could not be robustly estimated in people who cannot tolerate or are not eligible to have interferon treatment. At its second meeting, the Committee heard that mature observational data for simeprevir in combination with sofosbuvir would become available in the near future, and that this would include data on people who cannot tolerate or are not eligible to have interferon treatment. The Committee considered that it would be more appropriate to postpone making a decision on this combination until the more mature data become available. To avoid postponing the recommendations for the combination of simeprevir with peginterferon alfa and ribavirin for treating genotype 1 and 4 hepatitis C, the Committee recommended that this appraisal be split. Therefore, this appraisal no longer includes a recommendation for simeprevir in combination with sofosbuvir with or without ribavirin for treating people with genotype 1 and 4 HCV who are intolerant or ineligible for treatment with interferon.
4. Following a request from NHS England to extend the period during which funding must be made available, NICE consulted on a proposal to grant an extension to the deferred funding period until 31 July 2015. Following consideration of comments received during the consultation on a decision to amend the deferred funding, the NICE Guidance Executive decided that no extension to the normal period was required for simeprevir in combination with peginterferon alpha and ribavirin.  This is because simeprevir will be used in the same way as boceprevir and telaprevir. Both these interventions have been funded by the NHS since the publication of NICE appraisal guidance in early 2012. The resources and arrangements for safe delivery of treatment are already in place as a result of the availability of telaprevir and boceprevir.  Therefore, additional resources or training are not required to support the implementation of simeprevir. In addition, simeprevir treatment is less complex to administer than telaprevir and boceprevir, and the additional small patient population with genotype 4, for whom simeprevir is licensed is not expected to constitute a substantial challenge to the implementation.  Consequently, section 5 of the FAD states that clinical commissioning groups, NHS England and, with respect to their public health functions, local authorities are required to comply with the recommendations in this appraisal within 3 months of its date of publication.

About simeprevir

1.  Simeprevir (Olysio, Janssen) is a protease inhibitor; it inhibits the NS3/4A enzyme that the hepatitis C virus (HCV) depends on to replicate. Simeprevir is administered orally.
2. Simeprevir has a UK marketing authorisation in the UK for use in combination with peginterferon alfa and ribavirin or in combination with sofosbuvir (with or without ribavirin) for treating adults with genotype 1 or 4 chronic hepatitis C, including people with or without cirrhosis, and people with HIV.
3. For people who have not had previous treatment or whose disease has responded to previous treatment but subsequently relapsed, simeprevir in combination with peginterferon alfa and ribavirin is indicated for 12 weeks, followed by 12 weeks of peginterferon alfa and ribavirin alone.
4. For other people, the course of simeprevir is the same, but the course of pegylated interferon and ribavirin is longer than 24 weeks; specifically, for people whose disease did not respond to previous treatment, and for people with HIV who also have cirrhosis, simeprevir in combination with peginterferon alfa and ribavirin is indicated for 12 weeks, followed by 36 weeks of peginterferon alfa and ribavirin alone.
5. Simeprevir costs £1866.50 per pack of 7x150 mg tablets (excluding VAT, MIMS online, accessed July 2014). A course of simeprevir (for 12 weeks) plus peginterferon alfa and ribavirin (both for 24 weeks) costs £27,220. A course of simeprevir (for 12 weeks) plus peginterferon alfa and ribavirin (both for 48 weeks) costs £32,155.
6. For treating genotype 1 HCV, the ICERs for simeprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone was between £14,200 and £9800 per QALY. Simeprevir dominated both telaprevir and boceprevir (both with peginterferon alfa and ribavirin), that is simeprevir was less expensive and provided more QALYs.
7. The Committee noted that, in all scenarios for genotype 4 HCV, the ICERs for simeprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin remained below £20,000 per QALY gained. 

About chronic hepatitis C

1. 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.
2. 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.
3. 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.
4. A small percentage of people with chronic hepatitis C and cirrhosis also develop liver cancer.
5. For people with mild disease, a ‘watchful waiting’ approach may be agreed, on an individual basis, between the patient and clinician.
6. 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.
7. 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.
8. Shortened courses of peginterferon alfa and ribavirin are also recommended as an option for certain patient subgroups (NICE technology appraisal 200).
9. 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).

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[1] There are 6 major genotypes and several subtypes of the hepatitis C virus, the prevalence of each vary geographically. Genotypes 1 and 3 account for the majority of chronic hepatitis C cases in England (46% and 43% respectively). People with genotype 2 hepatitis C generally respond to treatment better than those with genotype 1, 3, 4, 5 or 6.
                           

 

 

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