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CAMBRIDGE, Mass., Jun 09, 2008 (BUSINESS WIRE) Vertex Pharmaceuticals Incorporated today announced
positive results from a planned interim analysis of PROVE 3, an
ongoing Phase 2b study evaluating telaprevir-based treatment in
patients with genotype 1 chronic hepatitis C virus (HCV) infection who
did not achieve sustained virologic response (SVR) with at least one
prior pegylated interferon (peg-IFN) and ribavirin (RBV) regimen.
Vertex is developing telaprevir in collaboration with Tibotec.
n the interim analysis, 52% (60 of 115; intent-to-treat analysis)
of patients randomized to receive treatment with a 24-week
telaprevir-based regimen (12 weeks of telaprevir in combination with
peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone)
maintained undetectable HCV RNA 12 weeks post-treatment (SVR 12). In
the interim analysis, adverse events were similar to those commonly
observed with peg-IFN and RBV including fatigue, nausea, rash,
headache, gastrointestinal disorders and anemia, and were consistent
with those previously reported in patients being treated with
telaprevir-based therapy in the PROVE 1 and 2 studies in
treatment-naive subjects.
Based on these data, Vertex and Tibotec plan to initiate a Phase 3
clinical trial in patients who have failed prior treatment with
peg-IFN and RBV. Telaprevir (TVR) is the most advanced HCV protease
inhibitor in clinical development targeting treatment of chronic
hepatitis C, and is in Phase 3 clinical development in treatment-naive
patients. Hepatitis C is a disease that afflicts more than 3 million
people in the United States alone, and 170 million worldwide.
Interim Analysis Results
PROVE 3 is a randomized, double-blind, placebo-controlled Phase 2b
study that enrolled patients who failed prior treatment with peg-IFN
and RBV. Patients enrolled in PROVE 3 included prior non-responders
(including null responders), prior relapsers and prior breakthroughs
to peg-IFN and RBV treatment. The interim analysis included 453
patients that were enrolled and received at least one dose of study
drug. In the interim analysis, 52% (60 of 115) of patients randomized
to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir
in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN
and RBV alone) achieved undetectable HCV RNA (less than 10 IU/mL;
Roche TaqMan) 12 weeks post-treatment (SVR12). Of the 115 patients, 66
were categorized as non-responders to prior treatment (defined as
patients who never achieved undetectable HCV RNA during prior
treatment, including null responders), 40 were prior relapsers
(defined as patients who had undetectable HCV RNA at the completion of
prior treatment, but relapsed during follow-up), and 9 were prior
breakthroughs (defined as patients who had viral rebound during prior
treatment). Among patients receiving the 24-week telaprevir-based
regimen, 41% (27 of 66) of the prior non-responders, 73% (29 of 40) of
prior relapsers, and 44% (4 of 9) of prior breakthroughs achieved SVR
12.
"Patients who have not achieved a sustained virologic response
with one or more courses of prior interferon-based therapy represent a
significant unmet medical need. These patients have few or no
available treatment options and they are at increased risk for
progressive liver disease," said John McHutchison, M.D., Principal
Investigator for the PROVE 3 Study and Associate Director of Duke
Clinical Research Institute.
A summary of available on-treatment and post-treatment antiviral
data from the 24-week telaprevir-based regimen is presented below:
Undetectable HCV-RNA by Response to Prior Peg-IFN/RBV Treatment (PROVE
3 24-week regimen; 12 weeks telaprevir+peg-IFN+RBV, followed by 12
weeks peg-IFN+RBV); intent-to-treat analysis
----------------------------------------------------------------------
Week 12 Week 24 (end SVR 12 (week 36;
of treatment) 12 weeks post-
treatment)
----------------------------------------------------------------------
Non-responders (n=66) 71% 65% 41%
----------------------------------------------------------------------
Relapsers (n=40) 88% 83% 73%
----------------------------------------------------------------------
Breakthroughs (n=9) 44% 44% 44%
----------------------------------------------------------------------
Total (n=115) 75% 70% 52%
----------------------------------------------------------------------
In the control arm (n=114), which is evaluating 48 weeks of
peg-IFN and RBV only, available data indicate that 8% of patients had
undetectable HCV RNA at week 12, and 30% had undetectable HCV RNA at
week 36 on-treatment (intent-to-treat analysis). In prior studies of
peg-IFN and RBV in treatment-failure patients, the proportion of
patients who had undetectable HCV RNA at week 36 of treatment has been
significantly higher than the proportion who ultimately achieved SVR.
End-of-treatment and post-treatment data (including SVR rates) are not
yet available for this study arm in PROVE 3.
In addition to the 24-week telaprevir-based regimen that includes
ribavirin and the 48 week control arm described above, two other
treatment regimens are being evaluated in PROVE 3: a 24-week
telaprevir treatment arm without ribavirin, and a 48-week treatment
arm that includes 24 weeks of telaprevir dosing in combination with
peg-IFN and RBV. The interim analysis supports the inclusion of
ribavirin in future studies of telaprevir-based regimens in
treatment-failure patients, similar to what has been observed in
treatment-naive subjects. In addition, available on-treatment results
suggest that additional dosing of telaprevir beyond 12 weeks does not
confer additional benefit to patients. Patient dosing has now been
completed in PROVE 3 and all patients are now being followed
post-treatment. Vertex anticipates that PROVE 3 data will be the
subject of a presentation at a medical conference later in 2008.
"These are the first data to show the potential of a STAT-C agent
to have this degree of antiviral response in patients--including both
non-responders and relapsers--who did not achieve SVR with prior
treatment. The interim data suggest that a telaprevir-based regimen
could be an important future treatment option for genotype 1 hepatitis
C patients who have failed a prior course of treatment," said John
Alam, M.D., Executive Vice President, Medicines Development, and Chief
Medical Officer of Vertex. "We are now planning to begin a Phase 3
clinical trial with telaprevir in patients who failed prior peg-IFN
and ribavirin treatment."
In the interim analysis, adverse events were similar to those
commonly observed with peg-IFN and RBV including fatigue, nausea,
rash, headache, gastrointestinal disorders and anemia, and were also
consistent with those previously reported in patients being treated
with telaprevir-based therapy in the PROVE 1 and 2 studies in
treatment-naive subjects. Thirteen patients (11%) receiving the
24-week telaprevir based treatment regimen (12 weeks of telaprevir in
combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and
RBV alone) discontinued treatment due to adverse events. The most
common reason for discontinuation among patients receiving this
24-week telaprevir-based treatment regimen was rash (7% of patients).
In the control arm, 5 patients (4%) discontinued treatment prior to
week 36 due to adverse events.
Phase 3 Study in Patients Who Failed Prior Treatment
Vertex and Tibotec plan to initiate a Phase 3 clinical trial in
genotype 1 HCV patients who have failed prior treatment with peg-IFN
and RBV in the third quarter, which will be led by Tibotec. The
randomized, double-blind and placebo-controlled study will focus on
regimens of 48 weeks total treatment duration, in which telaprevir is
administered for 12 weeks, with a goal of maximizing SVR rates. The
study is planned to be conducted at more than 50 centers in the U.S.,
E.U. and certain other countries.
Updates on the status of Vertex and Tibotec's clinical trials of
telaprevir are available at www.clinicaltrials.gov.
About PROVE 3
PROVE 3 is an ongoing, four-arm, Phase 2b clinical trial of 453
genotype 1 HCV patients who did not achieve an SVR with a prior course
of peg-IFN and RBV treatment. The study includes patients with
compensated cirrhosis. The study is assessing patients who receive
telaprevir-based treatment regimens of 24 and 48-week total duration,
compared to a 48-week control arm of peg-IFN and RBV. PROVE 3 is being
conducted at 50 clinical centers in the U.S. and the E.U.
About Telaprevir (VX-950)
Telaprevir (VX-950) is an investigational oral inhibitor of HCV
protease, an enzyme essential for viral replication, and is the most
advanced investigational agent in development that specifically
targets HCV. Telaprevir is the first hepatitis C protease inhibitor in
Phase 3 clinical trials. The Phase 3 ADVANCE trial is expected to
enroll 1,050 treatment-naive genotype 1 HCV patients and will evaluate
two 24-week telaprevir-based regimens in comparison to a 48-week
control arm. Vertex is also conducting a global Phase 2b clinical
development program of telaprevir, including PROVE 1 and PROVE 2 in
treatment-naive genotype 1 HCV patients, and PROVE 3 in genotype 1 HCV
patients who have not achieved SVR with a prior course of pegylated
interferon-based therapy.
Vertex retains commercial rights to telaprevir in North America.
Vertex and Tibotec are collaborating to develop and commercialize
telaprevir in Europe, South America, Australia, the Middle East, and
other countries. Vertex is collaborating with Mitsubishi Pharma to
develop and commercialize telaprevir in Japan and certain Far East
countries.
About Hepatitis C and Treatment-Failure Patients
Hepatitis C is a liver disease caused by the hepatitis C virus,
which is found in the blood of people with the disease. HCV, a serious
public health concern affecting 3.4 million individuals in the United
States, is spread through direct contact with the blood of infected
people. Though many people with HCV infection may not experience
symptoms, others may have symptoms such as jaundice, abdominal pain,
fatigue and fever. The burden of liver disease associated with HCV
infection is increasing, and current therapies typically provide
sustained benefit in less than half of patients with genotype 1 HCV,
the most common strain of the virus. As many as 250,000 patients in
the United States have received at least one course of treatment with
pegylated interferon and ribavirin but have not achieved SVR. Patients
who have failed interferon-based treatment typically have few or no
available treatment options, and are at risk for progessive liver
disease. In a recent study, the risk of liver failure, cancer or death
following unsuccessful HCV treatment was 23% after 4 years, and 43%
after 8 years. (1).
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
focused on viral diseases, inflammation, autoimmune diseases, cancer,
pain and cystic fibrosis. Vertex co-discovered the HIV protease
inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva (R) is a registered trademark of the GlaxoSmithKline group
of companies.
TaqMan(R) is a registered trademark of Hoffman-La Roche Inc.
1. Veldt et al, "Sustained virologic response and clinical
outcomes in patients with chronic hepatitis C and advanced fibrosis,"
Annals of Internal Medicine, 20 November 2007; 147: 677-684.
Safe Harbor Statement
This press release contains forward-looking statements, including
statements (i) that based on the interim results disclosed in this
press release Vertex and its collaborator plan to initiate a Phase 3
clinical trial in patients who have failed prior treatment with
peg-IFN and RBV, (ii) that available on-treatment results suggest that
additional dosing of telaprevir beyond 12 weeks does not confer
additional benefits to patients, (iii) that Vertex anticipates that
PROVE 3 data will be the subject of a presentation at a medical
conference later in 2008, (iv) that the interim data suggests that a
telaprevir-based regimen could be an important future treatment option
for genotype 1 hepatitis C patients who have failed a prior course of
treatment, (v) that based on this interim data, Vertex will be able to
demonstrate in PROVE 3 a significant difference in SVR rates with
telaprevir-based treatment compared to current treatments, in both
non-responders and relapsers, (vi) regarding the design of the Phase 3
clinical trial in treatment experienced patients that Vertex plans to
commence in the third quarter and (vii) regarding the Phase 3 ADVANCE
clinical trial that Vertex is conducting in treatment-naive patients.
While the Company believes the forward-looking statements contained in
this press release are accurate, there are a number of factors that
could cause actual events or results to differ materially from those
indicated by such forward-looking statements. Those risks and
uncertainties include, among other things, that (a) the promising
interim data from the PROVE 3 clinical trial, including the viral
response rates from 12 weeks post-treatment, will not be confirmed by
final data from the PROVE 3 treatment and control arms, which will
require viral response rates 24 weeks post-treatment, or by data
obtained from future clinical trials, (b) the outcomes for our planned
telaprevir clinical trials and studies may not be favorable, (c) the
commencement of future clinical trials may be delayed or the
anticipated trial design may need to be altered, (d) that there may be
varying interpretations of data produced by one or more of our
clinical trials, and (e) other risks listed under Risk Factors in
Vertex's annual report and quarterly reports filed with the Securities
and Exchange Commission and available through the Company's website at
www.vrtx.com. We disclaim any obligation to update the information
contained in this press release as new information becomes available.
(VRTX-GEN)
SOURCE: Vertex Pharmaceuticals Incorporated
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