The investigational hepatitis C viral (HCV) protease inhibitor VX-950 exhibits potent and sustained antiviral activity in vitro and has favorable pharmacokinetic properties, according to preclinical results presented by scientists from Vertex Pharmaceuticals. In addition, researchers reported that VX-950 retains full in vitro potency against HCV replicon strains resistant to another investigational HCV protease inhibitor currently being developed by another company. Vertex plans to initiate clinical studies of VX-950 in early 2004.

"As we prepare to advance VX-950 into initial clinical evaluation, these preclinical results provide important information that is in line with the treatment goal for this disease: clearing the hepatitis C virus from the liver," said John Alam, Senior Vice President, Drug Evaluation and Approval of Vertex. "Although significant progress has been made in recent years with combination therapy regimens, nearly half of HCV patients currently treated with the standard of care, pegylated interferon plus ribavirin, fail to achieve a sustained response. Direct antivirals represent the potential for a dramatic breakthrough in the treatment of HCV. HCV protease inhibitors, such as VX-950, could usher in a significant treatment advance for patients with HCV."

In a conference presentation entitled "VX-950: A Tight-Binding HCV Protease Inhibitor with a Superior Sustained Inhibitory Response in HCV Replicon Cells," virologist Ann Kwong, Head of Cell Biology and Infectious Disease at Vertex, reported the first data using an innovative adaptation of the HCV replicon assay commonly utilized to measure the potency of antiviral compounds against HCV. Vertex scientists used the HCV replicon assay system to evaluate how HCV protease inhibitors sustain potency over a period of four weeks. In these experiments, HCV replicon cells, which mimic the intracellular replication of HCV, were treated with VX-950 and were evaluated at multiple time points. In one experiment, treatment with VX-950 for nine days reduced HCV RNA by almost 10,000-fold (4 log10). In another experiment, HCV replicon cells treated with VX-950 for thirteen days exhibited viral clearance at day thirteen, and no rebound of HCV viral RNA was observed at day twenty-seven.

Dr. Kwong also described the development of a novel preclinical HCV protease expression model that was designed to stringently evaluate the ability of small molecule compounds to inhibit HCV protease in liver tissue. VX-950 dosed orally resulted in a significant, dose-dependent inhibition of an HCV-protease enzyme-dependent signal. In untreated control models, high concentrations of active HCV protease enzyme over seven days were associated with significant liver damage. However, treatment with VX-950 for the initial three days of the experiment resulted in sharply reduced liver damage. These data are the first to suggest that an HCV protease inhibitor may have a tissue-sparing effect on the liver. The mechanism by which this occurs is currently under investigation.