The potential role of simeprevir for the treatment of hepatitis C

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Date: Feb. 2015
From: Future Virology(Vol. 10, Issue 2)
Publisher: Future Medicine Ltd.
Document Type: Drug overview; Report
Length: 6,129 words
Lexile Measure: 1580L

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Author(s): Cristina del Barrio Gascón aff1 , Maria Buti [*] aff1

KEYWORDS

chronic hepatitis C; PEGylated IFN; ribavirin; simeprevir

Infection with HCV is a leading cause of liver disease worldwide [1 ]. An estimated 130-210 million people (3% of the global population) are currently infected, with an annual incidence of 2-4 million. Between 70 and 90% of acute infections become chronic and may lead to liver cirrhosis, chronic liver failure, hepatocellular carcinoma and death. Death related to the complications of cirrhosis in this population occurs at an annual rate of approximately 4%, whereas hepatocellular carcinoma occurs at a rate of 1-5%. Complications of chronic HCV infection have become the most common indication for liver transplantation [2 ].

HCV is classified into at least six major genotypes (designated 1-6) and many subtypes (a, b, c, and so on). Genotypes 1 to 3 have a worldwide distribution, and genotypes 1a and 1b are the most common, accounting for approximately 60% of all HCV infections, mainly in the USA, Europe and Japan. Genotype 3 is primarily endemic in Southeast Asia. Genotype 4 is most prevalent in the Middle East, North Africa and sub-Saharan Africa, but has recently spread to Europe and other parts of the world through immigration and injection drug use. Genotype 4 is responsible for more than 90% of HCV infections in Egypt, where it is associated with reuse of needles during mass administration of parenteral antischistosomal therapy up to the 1980s. Approximately 20% of people infected with HCV worldwide have HCV genotype 4. Genotype 5 is mainly found in South Africa and genotype 6 mainly in Asia [ 3 ].

About 30% of HIV-positive patients have HCV coinfection. The presence of HIV has been shown to accelerate the natural history of chronic hepatitis C in terms of progression to cirrhosis and end-stage liver disease. While morbidity and mortality secondary to opportunistic infections have decreased dramatically in this patient population with the introduction of highly active antiretroviral therapy, liver-related deaths have increased; hence, treatment of HCV has become a priority [4 ].

The combination of PEGylated inteferon (PEG-IFN) and ribavirin (RBV) has been the mainstay HCV treatment for many years. Nonetheless, the efficacy of PEG-IFN/RBV is unsatisfactory in some HCV genotypes or subpopulations (e.g., patients with cirrhosis) and the treatment is associated with considerable side effects, such as fatigue, influenza-like symptoms, gastrointestinal disturbances, neuropsychiatric symptoms and hematologic abnormalities [ 5 ].

In 2011, two direct-acting antiviral agents, telaprevir (TPV) and boceprevir, each administered in combination with PEG-IFN/RBV, were approved for the treatment of chronic HCV genotype 1 infection [6 ]. TPV and boceprevir are inhibitors of the HCV-encoded NS3/4A protease, which is an essential enzyme for viral replication, and in combination with PEG-IFN/RBV have demonstrated higher sustained virologic response (SVR) rates in treatment-naive and treatment-experienced populations than with PEG-IFN/RBV alone [7 ]. In addition, these combinations have been found to shorten overall treatment duration (from 48 weeks to 24-28 weeks) in a significant percentage of patients [8 ].

Nevertheless, SVR rates with TPV or boceprevir-containing...

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Gale Document Number: GALE|A407934438