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Press Release from Vertex Pharmaceuticals
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Vertex Researchers Report Data on HCV Protease Inhibitor VX-950
BOSTON, Oct. 27 /PRNewswire-FirstCall/ -- 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 at the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) held this week in Boston. 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, M.D., 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, Ph.D., 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. Additional data presented at the meeting by Vertex researchers demonstrated that the viral resistance profile of VX-950 is different from the resistance profile of the HCV protease inhibitor BILN-2061 in HCV replicon cells. VX-950 was able to inhibit HCV replicons containing the dominant mutation observed for BILN-2061 to the same degree as inhibition of wild type replicons. BILN-2061 is an investigational HCV protease inhibitor currently being developed by another company.
VX-950 is an oral, small molecule protease inhibitor discovered by Vertex using structure-based drug design. Vertex was the first to solve the structure of the hepatitis C NS3-4A protease domain, an enzyme that is essential for HCV viral replication. In addition to potent activity observed in vitro, preclinical testing conducted to date shows that VX-950 achieves excellent exposure in the liver, the target organ for HCV treatment, good oral bioavailability and favorable pharmacokinetic properties.
Chronic hepatitis C infection afflicts approximately 2.7 million people in the U.S., many of whom are unaware of the infection, which is often undetected for up to 20 years following initial infection. Worldwide, the disease strikes as many as 185 million people. HCV causes inflammation of the liver, which may lead to fibrosis and cirrhosis, liver cancer, and ultimately, liver failure. Each year, 8,000 to 10,000 people in the U.S. die from complications of HCV. Current treatments have been effective for only 40 to 60 percent of chronically infected HCV patients and are associated with significant side effects. At the present time, there are no direct antiviral therapies available for the treatment of HCV infection.
About Vertex Pharmaceuticals
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical partners. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the new HIV protease inhibitor Lexiva(TM) with GlaxoSmithKline.
Vertex Pharmaceuticals' Safe Harbor Statement
This press release may contain forward-looking statements, including statements that Vertex plans to initiate clinical studies of VX-950 in the stated timeframe. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause Vertex's actual results to vary materially. These risks and uncertainties include, among other things, the risk that i) VX-950 preclinical data may not be indicative of any future results; ii) Vertex's drug development programs may not proceed as planned due to partnership, technical or patient enrollment issues, and other risks listed under Risk Factors in Vertex's form 10-K filed with the Securities and Exchange Commission on March 31, 2003.
Lexiva(TM) is a registered trademark of the GlaxoSmithKline group of companies.
Vertex's press releases are available at www.vrtx.com.
References:
"VX-950: A Tight-Binding HCV Protease Inhibitor with a Superior Sustained Inhibitory Response in HCV Replicon Cells," Kwong, et al, Presentation, Hepatitis C: Therapy I Parallel Session, AASLD 2003
"VX-950, A HCV Protease Inhibitor, Retains Potency Against BILN-2061 Resistant Replicon Cells," Lin et al, Poster #1000, AASLD 2003
"VX-950: The Discovery of an Inhibitor of the Hepatitis C NS3-4A Protease and a Potential Hepatitis C Virus Therapeutic," Perni et al, Poster #972, AASLD 2003
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