BOSTON, Oct. 27 /CNW/ -- 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 (Nasdaq: VRTX - News) 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

	    Vertex Contacts:
	    Lynne H. Brum, Vice President, Corporate Development and Communications,
	    617-444-6614
	    Michael Partridge, Director, Corporate Communications, 617-444-6108
	    Michele Karpf Belansky, Associate Director, Corporate Brand Management,
	    On-site at conference: 617-510-5805, office: 617-444-6259

For further information

Lynne H. Brum, Vice President, Corporate Development and Communications, +1-617-444-6614, or Michael Partridge, Director, Corporate Communications, +1-617-444-6108, or Michele Karpf Belansky, Associate Director, Corporate Brand Management, On-site at conference: +1-617-510-5805, office: 617-444-6259, all of Vertex Pharmaceuticals

 

SAN DIEGO, Oct. 27 /PRNewswire/ -- Idun Pharmaceuticals, Inc. today announced positive data from its oral dose-ranging clinical trial of IDN-6556 for the treatment of liver impairment caused by Hepatitis C virus (HCV) infection. The data showed that when given orally, IDN-6556 normalized liver enzymes after just two weeks of twice-a-day dosing. Increased levels of aminotransferase enzymes are a well-accepted indicator of damage in the liver. As was seen in an earlier trial with an intravenous form of IDN-6556, the drug was safe and well tolerated, and did not appear to exacerbate the HCV infection. The data was presented by Paul Pockros, M.D., Head of the Division of Gastroenterology and Hepatology at Scripps Clinic (San Diego), at a late- breaking session of the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

 

"The data is encouraging," Dr. Pockros said. "Together with the other investigators in the trial, I believe the drug may be useful in treating a number of liver diseases and will be studied further in patients with HCV. The study is ongoing and we hope to present additional data next year on its effects in patients with other liver diseases, such as fatty liver disease (NASH) and hepato-biliary disease."

IDN-6556 is a potent inhibitor of the key caspase enzymes that mediate apoptosis and is designed to protect liver cells (hepatocytes) from excessive programmed cell death. Increased rates of apoptosis have been implicated in many different liver diseases. Unfortunately, individuals suffering from these conditions have limited treatment alternatives, many of which are often poorly tolerated, expensive and do not cure most patients.

The ongoing clinical trial is a double-blind, placebo-controlled, dose- ranging study being conducted at six major hepatology hospitals in the United States. The presentation was based on data from 41 patients, over 70% of whom had failed to have an adequate response with currently approved treatments of HCV (interferon-alpha and ribavirin).

"The study shows that IDN-6556 can have beneficial effects in as little as two weeks in patients with HCV," said David Shapiro, M.D., Idun's Chief Medical Officer. "The data from this study in HCV-infected patients provides support for the evaluation of the drug in its oral form in other liver diseases as well. We are currently developing the plans for the next set of clinical studies in patients with HCV. We plan to study the effects of the drug in both patients that have failed to be successfully treated with the currently available drugs and, separately, with IDN-6556 given together with such therapy."

"This data in humans is consistent with the results of extensive scientific research conducted by Idun and our collaborators," said Steven J. Mento, Ph.D., President and CEO of Idun. "It further supports our view that IDN-6556 may have a major impact on the treatment of a broad range of liver diseases and encourages us to proceed with an expanded development program."

Idun also recently announced the initiation of another clinical trial of IDN-6556 in patients undergoing liver transplantation.

Idun Pharmaceuticals, Inc. is a biopharmaceutical company located in San Diego, CA, creating innovative human therapeutics with a primary focus on controlling apoptosis, or programmed cell death. Apoptosis is a genetically controlled, normally occurring, biological process mediated by a cascade of intra-cellular proteins. Too much or too little apoptosis is believed to play a role in many important human diseases. Idun believes that its drug candidates will have utility in treating liver disease, inflammation, cancer, and cardiovascular disease. Idun has an extensive patent portfolio covering the fundamental and core technologies involved in the regulation of cell death.

Some of the statements in this press release are forward-looking statements and do not guarantee future performance and involve risks and uncertainties. Actual results may differ substantially from the results that the forward-looking statements suggest for various reasons. These forward- looking statements are made only as of the date of this press release.