Integration of in vitro data into a viral kinetics model to investigate
rapid development of Hepatitis C resistance to therapy
By Arthur Lo, PhD
Senior Scientist at Theravance
November 14, 2012
1:00 to 2:00 pm EST
Viral kinetics is a classic example of mathematical biology where insights
derived from the modeling have had significant impact on the understanding
and treatment of viral diseases causing chronic infection. The fundamental
structure of the viral kinetics model for HIV has been adapted to other
diseases such as Hepatitis B (HBV) and Hepatitis C (HCV), resulting in a
broader understanding of chronic viral infection.
The current search for approvable, interferon-free combination therapies for
HCV has led to significant investment in this area of research, with many
pharmaceutical companies developing therapies that target the virus with
different mechanisms of action.
The combination of available clinical data for these new therapies,
preclinical and clinical pharmacokinetic (PK) data and internal in vitro
data for comparable compounds has led to an opportunity where the models can
be refined to provide additional information that can be used to optimize
compound selection and predicted efficacy in comparison to the expected
standard of care.
I will describe the application of one approach to viral kinetics modeling
where preclinical and clinical data from competitor compounds has been
incorporated into a model that includes the dynamics of mutant strains of
virus. In addition, I will discuss how insights derived from the modeling
work have helped shape our understanding of internal candidate compounds and
helped to differentiate between competing compounds based on the predicted
ability to reduce the viral load in response to therapy in patients.
The purpose of the "Impact" series is to foster the use of M&S activities in
all phases of drug development by illustrating the advantages and enhancing
the applicability of M&S in product discovery, development, and marketing
programs.
The series is intended for drug development project team members from
discovery to phase 4 clinical trials. This includes pharmacologists, ADME
scientists, PK/PD modelers, clinical pharmacologists, clinical development
team members, regulatory affairs specialists, and other interested
professionals.
Register for this free webinar at www.rosaandco.com/webinar. After
registering you will receive a confirmation email containing information
about joining the webinar. More information about the webinar series, an
archive of past webinars, and a list of future webinar speakers may be found
at www.rosaandco.com/webinar.
Please allow 5-10 minutes for a Java applet to be installed on your computer
prior to joining our webinar series for the first time.
Toufigh Gordi
Toufigh Gordi, PhD
President, PK/PD and Clinical Pharmacology Services
Direct: 408-480-7314
Corp: 408-370-9800
Fax: 408-370-9810
[email protected]