Chemistry Reference
In-Depth Information
CHAPTER 11
2
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-F-2
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-C-Methyl Nucleosides
and Nucleotides for the
Treatment of Hepatitis C Virus:
from Discovery to the Clinic
MICHAEL J. SOFIA, PHILLIP A. FURMAN AND
WILLIAM T. SYMONDS
Pharmasset, Inc., 303A College Road East, Princeton, NJ 08540, USA
11.1 Introduction
The hepatitis C virus (HCV) infects approximately 170 million individuals
worldwide, and
80% of those infected will develop chronic liver infection.
1
Of those chronically infected with HCV,
B
25% will develop liver cirrhosis and
approximately 10% will go on to develop hepatocellular carcinoma.
2
The
current treatment regimen for HCV-infected patients consists of regular
injections of pegylated interferon (IFN) in combination with oral ribavirin
(RBV) administration. However, this combination therapy is only effective in
producing a sustained virological response in 40-60% of treated patients.
Moreover, severe side effects, including flu-like symptoms, fatigue, hemolytic
anemia, and depression, result in a high rate of drug discontinuations.
3,4
Consequently, due to the limited ecacy and intolerable side effects of the
current standard of care (SOC), the need for the development of effective small-
molecule, direct-acting antiviral agents is great.
B
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