-- Five Patients on 14-day Clinical Study Achieve Plasma Levels
Below Limit of Quantitation --
CHICAGO, May 17 /PRNewswire-FirstCall/ -- In an oral presentation today at
the Digestive Disease Week conference, Henk W. Reesink, M.D., Associate
Professor of Medicine at Academic Medical Center in Amsterdam, presented
results of a Phase Ib clinical trial with the oral hepatitis C virus (HCV)
protease inhibitor VX-950, an investigational drug discovered by Vertex
Pharmaceuticals Incorporated (Nasdaq: VRTX). In the study, dosing with VX-950
for 5 and 14 days was well-tolerated in both healthy volunteers and in
patients with chronic HCV infection. In addition, patients treated with 750
mg of VX-950 every eight hours achieved a median reduction of HCV-RNA of 4.4
log10, equivalent to a 25,000-fold reduction in viral levels, at the end of 14
days of treatment. At the end of 14 days of treatment, 4 of 8 patients in the
750 mg dose group tested HCV-RNA negative in the quantitative Roche COBAS
TaqMan(R) assay (<30 IU/mL); 2 of these 4 patients tested undetectable in the
qualitative Roche TaqMan(R) assay (limit of detection 10 IU/mL). A patient in
another VX-950 dose group also achieved plasma HCV-RNA below the limit of
quantitation by the end of treatment. All patients in the clinical trial had
genotype 1 HCV infection, the most difficult strain to treat, and were either
non-responsive to prior treatment or treatment-naive. VX-950 is one of the
most advanced of a new class of direct antivirals for hepatitis C.
"Preliminary results from this early Phase Ib clinical study suggest that
the investigational drug VX-950 produces a rapid and profound reduction in
HCV-RNA as a single agent," said Prof. Reesink. "In the best dose group in
the Phase Ib clinical study, VX-950 reduced HCV viral load in some patients to
below the limit of detection of the most sensitive assays in two weeks. VX-950
was also well-tolerated in this study. These data further support the view
that HCV protease is the most potent single mechanism for suppressing
hepatitis C viral replication."
"The antiviral effect of VX-950 in this first study has exceeded our
expectations," said Joshua Boger, Ph.D., Chairman, President and Chief
Executive Officer of Vertex Pharmaceuticals. "The rapidity of viral load
decline and the achievement of viral levels to below detection in some
patients means that we have a broad opportunity to explore VX-950 in more
advanced studies in hepatitis C patients. Vertex is committed to moving as
rapidly as possible to advance VX-950 to the next stage of clinical
development."
Key Phase Ib Study Findings
Significant reductions in HCV-RNA were observed in HCV patients taking VX-
950 across three dose groups -- 450 mg every 8 hours, 1250 mg every 12 hours,
or 750 mg every 8 hours -- over a period of 14 days. Within three days of
treatment, the median reduction in HCV-RNA was greater than 3 log10, a
reduction of at least 1,000-fold, in all three VX-950 dose groups. In the
dose group receiving 750 mg of VX-950 every 8 hours, there was a further
reduction in viral levels between days 3 and 14 of treatment, with a median
HCV-RNA reduction of 4.4 log10 at day 14. Trough VX-950 plasma concentrations
were highest in the 750 mg every 8 hour dose group. At the end of treatment,
4 of 8 patients in the 750 mg dose group tested HCV-RNA negative in the
quantitative Roche COBAS TaqMan(R) assay (<30 IU/mL), and 2 of these 4
patients tested undetectable in the qualitative Roche COBAS TaqMan(R) assay
(limit of detection 10 IU/mL).
At the end of dosing, a total of 5 patients in the Phase Ib study across
the dose groups tested HCV-RNA negative in the quantitative Roche COBAS
TaqMan(R) assay (<30 IU/mL), reaching this level sometime between day 11 and
14. Following completion of the 14-day dosing period, a slow increase in HCV-
RNA levels was observed during a 28-day post-dosing period in these patients.
Twenty-eight days after receiving their last dose of VX-950, there were two
patients that had viral levels of more than 1 log10 below their pre-treatment
levels.
Preliminary data indicate that across the three dose groups, VX-950 was
well-tolerated, with no serious adverse events or treatment discontinuations
reported. In addition, no elevations of ALT/AST or other clinical chemistry
findings were reported.
About VX-950
VX-950 is an oral inhibitor of hepatitis C virus protease, an enzyme
essential for viral replication. Vertex completed a Phase Ia clinical study
of VX-950 in healthy volunteers in 2004, which indicated that VX-950 was well-
tolerated in ascending single doses up to 1250 mg. Pharmacokinetic results
from the Phase Ia study suggested that VX-950 can achieve liver concentrations
substantially greater than IC50 and IC90 observed in non-clinical studies.
Preclinical studies, presented at various medical conferences in 2003 and
2004, demonstrated that VX-950 significantly reduces levels of HCV RNA in both
an in vitro replicon system and infectious virus assays. Vertex researchers
were the first to solve the three-dimensional crystal structure of HCV
protease, and have used structural insights to enable the design of small
molecule HCV protease inhibitors, including VX-950.
Next Steps
The Company is actively planning more advanced studies to evaluate VX-950
as monotherapy and in combination with other HCV treatments. Vertex plans to
consult with the U.S. FDA and European regulatory authorities on the Company's
development plans. Vertex expects to file an investigational new drug (IND)
application in the second half of 2005 to support Phase II clinical
development of VX-950 in the United States. In collaboration with Vertex,
Mitsubishi Pharma Corporation is developing VX-950 in Japan and certain Far
East countries.
Web Cast Conference Call on May 17
Vertex Pharmaceuticals will host a conference call on May 17, 2005 at 4:00
p.m. Eastern Time (EDT) to review results from the Phase Ib clinical trial of
VX-950. This call will be broadcast via the Internet at http://www.vrtx.com in the
investor center and will be available until end of day on May 31, 2005.
Alternatively, to listen to the call live on the telephone, dial (800) 374-
0296 (U.S. and Canada) or (706) 634-2224 (International).
The archived call will be available via telephone commencing May 17, 2005 at
8:00 p.m. EDT through 5:00 p.m. EDT on May 24, 2005. The replay phone number
for the U.S. and Canada is (800) 642-1687. The international replay number is
(706) 645-9291. The conference ID number is 6231209 for both numbers.
Background
Phase Ib Trial Design: Healthy Volunteers
The Phase Ib clinical trial involved dosing of VX-950 in healthy volunteers as
well as patients chronically infected with genotype 1 HCV. Initially, 24
healthy volunteers were randomized to receive one of three doses of VX-950 -
450 mg every 8 hours, 750 mg every 8 hours; or 1250 mg every 8 hours - or
placebo, for five days. The purpose of dosing in healthy volunteers was to
evaluate the safety and pharmacokinetics of multiple doses of VX-950 before
proceeding to dosing in patients.
Healthy Volunteer Results
Full analysis of the data in healthy volunteers has been completed. No
serious adverse events or treatment discontinuations were reported. The most
common adverse events considered to be possibly related to study drug were
headache (5 of 24 subjects), diarrhea (3 subjects), nausea (2 subjects),
frequent urination (2 subjects) and sleepiness/drowsiness (2 subjects); all
were mild in severity. No changes were observed in vital signs, physical
examinations, or heart rhythm and electrical intervals (as measured by digital
ECGs).
Phase Ib Trial Design: HCV Patients
Double-blind, randomized placebo-controlled dosing of VX-950 in HCV
patients was then conducted to evaluate the tolerability, pharmacokinetics and
effect on viral kinetics of three doses of VX-950 - 450 mg every 8 hours; 1250
mg every 12 hours, or 750 mg every 8 hours. Each dose was administered over a
period of 14 days, with additional post-treatment follow-up. A key goal of
this portion of the study was to assess different dosing levels and
frequencies for VX-950 to provide insight into dose selection for future
monotherapy and combination therapy studies. Thirty-four patients with
chronic genotype 1 hepatitis C virus infection were enrolled in the study.
Six patients received placebo and 28 patients received VX-950. The study was
conducted at three centers in Europe. The trial enrolled 25 patients who were
non-responders to prior interferon-based regimens, and 9 patients who were
treatment-naive. In the HCV patient dosing portion of the study, patient
demographics were similar across the three dose groups. Median serum viral
load at study entry ranged between 6.13 log10 and 6.48 log10 HCV-RNA
(approximately 1.5- 3 million IU/mL).
Vertex continues to evaluate data from the Phase Ib clinical study.
Complete analyses of the safety and tolerability of VX-950, as well as
pharmacokinetic and viral sequencing analyses for all patients, are underway.
About Vertex
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
companies. Vertex's product pipeline is principally focused on viral
diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes
the HIV protease inhibitor, Lexiva(R), with GlaxoSmithKline.
Lexiva(R) is a registered trademark of the GlaxoSmithKline group of
companies.
Vertex's press releases are available at http://www.vrtx.com
About Digestive Disease Week
Digestive Disease Week (DDW) is the largest international gathering of
physicians, researchers and academics in the fields of gastroenterology,
hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the
American Association for the Study of Liver Diseases (AASLD), the American
Gastroenterological Association (AGA), the American Society for
Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the
Alimentary Tract (SSAT), DDW takes place May 14-19, 2005 in Chicago. The
meeting showcases approximately 5,000 abstracts and hundreds of lectures on
the latest advances in GI research, medicine and technology.
Safe Harbor Statement
This press release may contain forward-looking statements, including
statements that (i) Vertex's HCV protease inhibitor VX-950 is well-tolerated
and produces rapid and profound reduction in HCV-RNA as a single agent; (ii)
that Vertex expects to explore development of VX-950 as monotherapy and as
part of combination therapy; (iii) protease inhibitor-based therapy has the
potential to become a powerful option in future HCV therapy; and (iv) Vertex
plans to file an IND during the second half of 2005 to support clinical
development of VX-950 in the United States. 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 risks that (i) full analysis of the data, or further
testing, will not reflect the interim results, or support any or all of the
conclusions provided in this press release; (ii) clinical trials for VX-950
may not proceed as planned due to technical, scientific, or patient enrollment
issues, clinical trial results may not be available when expected, or expected
regulatory filings may not occur or may be delayed due to adverse clinical or
non-clinical trial developments; (iii) further clinical trials will not
confirm the potential of VX-950 for the treatment of HCV infection; and other
risks listed under Risk Factors in Vertex's Form 10-K filed with the
Securities and Exchange Commission on March 16, 2005.
Vertex Contacts:
(Chicago) Contacts:
Lynne Brum, VP, Corporate Communications and Financial Planning,
(617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Lora Pike, Manager, Investor Relations, (617) 444-6755
(Cambridge) Contacts:
Katie Burns, Manager, Investor Relations, (617) 444-6656
Zachry Barber, Specialist, Media Relations, (617) 444-6470
SOURCE Vertex Pharmaceuticals Incorporated
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Related links:
http://www.vrtx.com
Company News On-Call:
http://www.prnewswire.com/comp/938395.html
CONTACT:
Lynne Brum, VP, Corporate Communications and
Financial Planning, +1-617-444-6614, or Michael Partridge,
Director, Corporate Communications, +1-617-444-6108, or Lora
Pike, Manager, Investor Relations, +1-617-444-6755, or Katie
Burns, Manager, Investor Relations, +1-617-444-6656, or Zachry
Barber, Specialist, Media Relations, +1-617-444-6470
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