Merck Research Laboratories, West Point, Pennsylvania 19486, USA. Daria_hazuda@merck.com
The identification of hepatitis C virus (HCV) as the causative agent of non-A and non-B hepatitis, over 20 years ago, fueled an intensive effort to develop direct-acting antivirals targeting the viral polymerase and protease, two key proteins critical for HCV replication. However, it took more than two decades for these efforts to be realized with boceprevir, one of the two HCV protease inhibitors approved for treatment of HCV infection in 2011. The development of boceprevir is a major advancement in the ability to treat HCV infection and a significant step toward the long-term goal of eradicating chronic HCV infection. Both as a first-in-class agent and an entirely new modality for treating HCV infection, many challenges were encountered during the discovery and development of this compound. The lessons learned in overcoming these obstacles offer insights and pave the way for the newly emerging field of HCV antiviral therapeutics. This paper will describe the discovery and development of a first-in-class direct antiviral treatment for chronic hepatitis C infection, boceprevir, marketed around the world as Victrelis™.