Research Findings Suggest Potent Antiviral Activity and Favorable In Vitro Resistance Profile for Vertex's Investigational HCV P
October 27 2003 - 3:00PM
PR Newswire (US)
Research Findings Suggest Potent Antiviral Activity and Favorable
In Vitro Resistance Profile for Vertex's Investigational 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 http://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
http://www.newscom.com/cgi-bin/prnh/20000119/VERTEXLOGO
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http://photoarchive.ap.org/ DATASOURCE: Vertex Pharmaceuticals
CONTACT: 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 Web site: http://www.vrtx.com/ Company News
On-Call: http://www.prnewswire.com/comp/938395.html
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