Pedro Gulln Tosio

Memorandum Hepatitis C and the new treatments

MEMORANDUM
To

Pilar Farjas Abada

General Secretary of Health
Ministry of Health, Social Service and Equality.
From
Pedro Gulln Tosio
Director of Health Planification.
National School of Public Health.
Carlos III Health Institute (ISCIII)
CC
Ana Mato
Minister of Health, Social Service and Equality
Ministry of Health, Social Service and Equality.
Subject Hepatitis C and the new treatments

Summary and purpose

Hepatitis C is an important public health issue, as is one of the leading causes of chronic
liver disease, cirrhosis and liver cancer. New drug agents against Hepatitis C have been
proved as highly effective for those patients. The purpose of this memorandum is to
provide information and evidence of the effectiveness and cost-effectiveness of Hepatitis C
drugs in order to decide the public funding of the new Hepatitis C treatment.

Epidemiology of Hepatitis C
Hepatitis C is a liver disease caused by the Hepatitis C virus; the virus can cause both acute
and chronic hepatitis infection. Its consequences range in severity from a mild illness
lasting a few weeks to a serious, lifelong chronic disease.
25 years after the identification of the Hepatitis C virus, it still continues as a major Global
Health issue. Hepatitis C is found worldwide. The most affected regions are Central and
East Asia and North Africa. Hepatitis C virus infection prevalence varies between 0.4 and
3.5% of the population in different European Union countries. It is estimated that 1.6% to
2.9% of Spanish population is infected with Hepatitis C virus1. The disease can remain
dormant for years and then cause cirrhosis or liver cancer. Hepatitis C chronic disease is
the leading cause of liver transplant, although it can recur in the transplanted liver.
The hepatitis C virus is a bloodborne virus. It is most transmitted through injecting drug
use through the sharing of injection equipment; in health care settings due to the reuse or
inadequate sterilization of syringes and needles; a years ago in Spain, and in developing
countries now, HCV is transmitted via the transfusion of unscreened blood and blood
products; HCV can also be transmitted sexually, and can be passed from an infected
mother to her baby; however these modes are less common.

Muoz-Gmez JA, Salmern J. Prevalence of hepatitis B and C in Spain: further data are needed. Revista Espaola de
Enfermedades Digestivas 2013;105:245-8.
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Pedro Gulln Tosio

Memorandum Hepatitis C and the new treatments
Of each 100 persons infected with HCV, 75 to 85 will develop chronic infection; 60-70 will
develop chronic liver disease; 5-20, cirrhosis; and 1-5 will die of cirrhosis or liver cancer. 2

Available treatments for Hepatitis C.

Hepatitis C does not always require treatment as the immune response in some people
will clear the infection. Until recently, the standard of care for chronic HCV infection
involved combination therapy with pegylated interferon and ribavirin.
Scientific advances have led to the development of new antiviral drugs for hepatitis C,
which are much more effective, safer and better-tolerated than existing therapies. These
therapies, known as oral directly acting antiviral agent (DAAs) therapies simplify hepatitis
C treatment by significantly decreasing monitoring requirements and by increasing cure
rates. Although the production cost of DAAs is low, the initial prices set by companies are
very high and likely to make access to these drugs difficult even in high-income countries.

a) Pegylated interferon + ribavirin

The current standard treatment for hepatitis C is combination antiviral therapy with
interferon and ribavirin, which are effective against all the genotypes of hepatitis viruses
(pan-genotypic). For genotype 1 disease, this resulted in a sustained viral response (SVR)
in approximately 4050% of patients3, which in turn results in lower rates of liver-related
morbidity and mortality. For genotypes 2 and 3, there is more than 80% of success with
the 6 months treatment3.
2

Unfortunately, interferon is not widely available globally and it is poorly tolerated in some
patients. This means that management of the treatment is complex, and many patients do
not finish their treatment. Despite these limitations, interferon and ribavirin treatment
can be life-saving.

b) DDAs therapies
Treatment with the DDA telaprevir or boceprevir, given in combination with pegylated
interferon and ribavirin, have been shown to significantly improve SVR both in treatmentnatve and in treatment-experienced patients with genotype 1 disease as the success rise
from 40-50% to 66-75%4. As these treatments are cost-effective5, both USA and and
England and Wales NICE, recommend triple therapy as the new standard of care for
patients with genotype 1 infection. In Spain, the Spanish Medicine Agency (AEMPS)
recommend triple therapy for patients with advanced liver fibrosis.
New DDA drugs
New drugs have appeared in the last months. Sofosbuvir has shown to be safe and close to
100% effective (83-100%) for treating all genotypes of Hepatitis C, as it is settled in a
recent paper published in the New England Journal of Medicine. 6 This important
http://www.who.int/mediacentre/factsheets/fs164/en/
3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus
ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-65.
4 Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection.
New England Journal of Medicine 2011;364:2405-16
5 Blazquez-Perez A, San Miguel R, Mar J. Cost-effectiveness analysis of triple therapy with protease inhibitors in treatmentnaive hepatitis C patients. PharmacoEconomics 2013;31:919-31.
6 Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus Sofosbuvir for Previously Treated or Untreated
Chronic HCV Infection. New England Journal of Medicine 2014;370:211-21
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Pedro Gulln Tosio

Memorandum Hepatitis C and the new treatments
achievement for Hepatitis C patients have been approved recently by the US Food and
Drugs Administration (FDA) and by the European Medicines Agency (EMA).
As this progress can be the most important scientific advance for Hepatitis C patients, it is
important to know if this treatment can be funded by the Spanish National Health System.
The main drawback of these new agents is the huge price tag (120000-180000 per
person treated), which will make treatment out of reach for people not only in the
developing countries, but to developed countries too.
As treatment options for chronic HCV infection expand, it will be important to understand
the cost reductions associated with achievement of a Sustained Viral Response, in addition
to the obvious clinical benefits to an individual patient. DDAs drugs for Hepatitis C have
been shown highly cost-effective for patients in advanced liver fibrosis (F3/F4),7 so it can
be recommended prioritize those patients.
Based on the fact that the new hepatitis C treatments are comparable in molecular
structure and chemistry to HIV antiretroviral, it can be estimated that the minimum cost
to manufacture these drugs is $100250 per 12 week treatment course8; at these low
prices, widespread access to these new medicines is feasible within 15 years.
Much needs to be done to ensure that these advances lead to greater access to treatment
globally.

Conclusions and recommendation

There is strong evidence to support the use of new DDA drugs for Hepatitis C patients.
Supported by evidence, we urgently encourage AEMPS to authorize the use of Sofosbuvir.
We therefore recommend the public funding of the new Hepatitis C drugs for patients with
F3 and F4 liver fibrosis.

We are available to answer any questions you may have about this topic. You can contact
us by e-mail: pgullon@isciii.es

Pedro Gulln Tosio

Director of Health planification.
National School of Public Health
Carlos III Institute of Health (ISCIII)

7 Obach D, Deuffic-Burban S, Esmat G, et al. Effectiveness and Cost-effectiveness of Immediate Versus Delayed Treatment of
Hepatitis C VirusInfected Patients in a Country With Limited Resources: The Case of Egypt. Clinical Infectious Diseases
2014;58:1064-71.
8 Hill A, Khoo S, Fortunak J, Simmons B, Ford N. Minimum costs for producing Hepatitis C Direct Acting Antivirals, for use in
large-scale treatment access programs in developing countries. Clinical Infectious Diseases 2014