Modeling HCV antivirals

Friday, October 26, 2007 - 1:25pm - 2:25pm
Vincent 570
Jeffrey Saltzman (Merck & Co., Inc.)
Hepatitis C affects between 4 and 5 million people in the United States
with nearly 75% suffering chronic infection. Further, current estimates
indicate 170 million people are infected, worldwide, with the Hepatitis
C virus (HCV). Pegylated interferon and ribavirin combination therapy is
currently the standard of care for treatment of HCV but is considered
less than optimal. For example, sustained virologic response (SVR) for
genotype 1 virus is observed in pivotal clinical trials for only 54% of
treated patients. SVR is defined as undetectable HCV RNA in plasma on
the order of 6 months after cessation of treatment. This combination
therapy is also associated with a high incidence of significant side
effects suffered over a treatment interval of at least six months.
Identification of better treatment alternatives is the goal of a
vigorous antiviral program at Merck.

In this talk we describe mathematical models explaining HCV infection
and response to treatment. The model equations and resultant
simulations were chiefly derived from the literature. Simulations have
already provided support for the antiviral drug development program at
Merck. Mathematical modeling gives evidence of target engagement and
drug efficacy. Using accumulated simulation experience gained from basic
research, preclinical data, and the literature, design optimizations for
early clinical studies may be proposed. As internal modeling expertise
is enhanced by experience gained in early development, this mathematical
knowledge base may help optimize costly phase III trials by guiding key
decisions such as dose selection and length of dosing.