- PROVE 1 & PROVE 2 Studies Expected to Enroll 580 Patients -
CAMBRIDGE, Mass., May 23 /CNW/ -- Vertex Pharmaceuticals
Incorporated (Nasdaq: VRTX) today reported that it has initiated PROVE 1, a
major Phase II study of VX-950, an investigational oral hepatitis C virus
(HCV) protease inhibitor. In addition, the Company today announced it expects
to initiate PROVE 2, a second major Phase II study in June. The studies will
be conducted in the United States and Europe as part of a global Phase II
development program for VX-950. Together, the two studies are expected to
evaluate sustained viral response (SVR) rates in 580 treatment-naive patients
infected with genotype 1 HCV.
Vertex's global Phase II development program in treatment-naive patients
has three objectives: to evaluate the optimal SVR rate that can be achieved
with VX-950 therapy in combination with the current standard of care, to
evaluate the optimal treatment duration for VX-950, and to evaluate the role
of ribavirin in VX-950-based therapy. In addition to these two major studies,
Vertex expects to begin additional clinical studies of VX-950 in the second
half of the year, including a Phase IIb study in patients who failed prior
standard of care treatment. Vertex anticipates this Phase IIb study to enroll
approximately 400 patients. By the end of the first quarter of 2007, Vertex
expects to have enrolled approximately 1,000 patients in clinical trials of
VX-950.
"PROVE 1 is the largest clinical study to date of an HCV protease
inhibitor in triple combination therapy in a treatment-naive patient
population, and provides us with the first opportunity to assess the potential
to enhance sustained virologic response rates with a shortened treatment
duration with VX-950, along with peginterferon and ribavirin," said John
McHutchison, M.D., Duke University and Lead Investigator for the PROVE 1
study. "Throughout this Phase II study, we will further develop a clinical
and safety database and increase our experience with VX-950 among clinicians
and patients."
VX-950 Program Update
PROVE Studies
The two studies announced today are the initial studies in a program of
the "Investigation of HCV Protease Inhibition for Viral Eradication" (PROVE).
The PROVE 1 and PROVE 2 studies have been designed as major, complementary
studies to be conducted in the United States and Europe that will evaluate the
ability of VX-950 to achieve SVR with short duration combination therapy.
Following consultations with regulatory authorities in the U.S. and Europe,
trial designs have been completed. Vertex expects the PROVE 1 and PROVE 2
studies to enroll 580 patients at more than 55 centers worldwide. Vertex
expects that these studies, taken together, will provide a substantial
evaluation of the potential of VX-950-based therapy to achieve SVR.
Phase II Studies for VX-950
Treatment Regimen Patients in Patients in
PROVE 1 PROVE 2 TOTAL
12-week regimens of VX-950 in
combination with pegylated
interferon (peg-IFN) and
ribavirin (RBV) 20 80 100
12-week regimens of VX-950 in
combination with only peg-IFN 0 80 80
12-week regimens of VX-950 in
combination with peg-IFN and
RBV, followed by 12 weeks of
therapy with peg-IFN and RBV 80 80 160
12-week regimens of VX-950 in
combination with peg-IFN and
RBV, followed by 36 weeks of
therapy with peg-IFN and RBV 80 0 80
Standard of Care HCV Treatment 80 80 160
Total 260 320 580
PROVE 1 Study in the U.S.
Vertex has initiated in the U.S., a four-arm, 260-patient Phase II study
of VX-950 known as PROVE 1. The first dosing of patients will occur in June.
The primary objective of this study is to assess the proportion of patients in
each study arm who achieve SVR, defined as undetectable (less than 10 IU/mL,
as measured by the Roche TaqMan(R) assay) HCV RNA 24 weeks after the
completion of dosing. In the study, there will be an initial randomization of
80 patients equally across all four treatment arms. There will be a second
randomization of an additional 180 patients across three treatment arms
focused on 24 and 48 weeks of therapy. The study will be conducted in
approximately 35 centers in the U.S. The study arms include:
12 weeks of therapy, with VX-950 dosed at 750 mg every eight hours
(q8h) in combination with standard doses of pegylated-interferon
(peg-IFN) and ribavirin (RBV); or
24 weeks of therapy, with VX-950 dosed at 750 mg every eight hours
(q8h) in combination with standard doses of peg-IFN and RBV for
12 weeks, then continuing for another 12 weeks with peg-IFN and RBV
alone; or
48 weeks of therapy, with VX-950 dosed at 750 mg every eight hours
(q8h) in combination with standard doses of peg-IFN and RBV for
12 weeks, then continuing for another 36 weeks with peg-IFN and RBV
alone; or
A control arm with peg-IFN and RBV dosed for 48 weeks
Patients in the 12 and 24-week treatment arms who achieve a rapid viral
response (RVR) defined as undetectable (less than 10 IU/mL) viral levels by
the end of week 4, and who maintain this status through to either week 10 or
20 respectively, will stop all treatment at the 12 or 24-week time point and
will be followed post-treatment to evaluate whether they achieve SVR.
Patients in these treatment arms who do not meet the RVR criterion will
continue on peg-IFN and RBV for a total duration of 48 weeks. The 48-week
treatment arm that contains VX-950 will evaluate whether 36 weeks of
additional treatment with peg-IFN and RBV adds substantially to the SVR rate
compared to 12 weeks of additional treatment with peg-IFN and RBV.
PROVE 2 Study in Europe
In June, Vertex will initiate in Europe, a four-arm, 320-patient Phase II
study of VX-950, known as PROVE 2. The primary objective of this study is to
assess the proportion of patients in each study arm who achieve SVR, defined
as undetectable (less than 10 IU/mL) HCV RNA 24 weeks after the completion of
dosing. In the study, 320 patients will be randomized equally across all
four treatment arms, providing a total of 80 patients per arm. The study will
be conducted in more than 20 centers in Europe. The study arms include:
12 weeks of therapy, with VX-950 dosed at 750 mg every eight hours
(q8h) plus a standard dose of pegylated-interferon (peg-IFN); or
12 weeks of therapy, with VX-950 dosed at 750 mg every eight hours
(q8h) plus standard doses of peg-IFN and ribavirin (RBV); or
24 weeks of therapy, with VX-950 dosed at 750 mg every eight hours
(q8h) plus standard doses of peg-IFN and RBV for 12 weeks, then
continuing for another 12 weeks with peg-IFN and RBV alone; or
A control arm with peg-IFN and RBV dosed for 48 weeks
As in the PROVE 1 study, patients in the 12 and 24-week treatment arms who
achieve a rapid viral response (RVR) defined as undetectable (less than 10
IU/mL) viral levels by the end of week 4, and who maintain this status through
to either week 10 or 20 respectively, will stop all treatment at the 12 or 24-
week time point and will be followed post-treatment to evaluate whether they
achieve SVR. Patients in these treatment arms who do not meet the RVR
criterion will continue on peg-IFN and RBV for a total duration of 48 weeks.
The 24-week treatment arm will evaluate whether 12 weeks of additional
treatment with peg-IFN and RBV adds substantially to the SVR rate compared to
12 weeks of VX-950 in combination with peg-IFN and RBV.
Additional Studies
In addition, Vertex expects to further broaden the VX-950 development
program to evaluate VX-950 in other treatment regimens and patient
populations. In the second half of the year, Vertex plans to initiate a Phase
IIb study in patients who failed prior standard of care treatment. Vertex
anticipates this Phase IIb study to enroll approximately 400 patients. The
Company also expects to begin a multi-dose, drug-drug interaction study of VX-
950 and low-dose ritonavir in the second half of this year. By the end of the
first quarter of 2007, Vertex expects to have enrolled approximately 1,000
patients in clinical trials of VX-950.
"In clinical trials to date, VX-950 has consistently demonstrated rapid
and dramatic reductions in HCV RNA levels," said John Alam, M.D., Executive
Vice President of Medicines Development and Chief Medical Officer for Vertex.
"We believe the 2006 global Phase II program will establish VX-950's clinical
profile by answering key questions about SVR rates, treatment duration and the
role of ribavirin. We will receive the first clinical data from this global
Phase II program starting in Fall 2006."
Data Presentations for VX-950
On May 21, 2006, Vertex announced results for a 28-day, Phase II study of
VX-950 in combination with peg-IFN and RBV at the Digestive Disease Week(R)
(DDW(R)) Conference in Los Angeles, California, which showed that plasma HCV
RNA levels were below the limit of detection (10 IU/mL) in 12 of 12 patients
at the end of 28 days of treatment with VX-950 in combination with peg-IFN and
RBV. Researchers also reported that 11 of these patients continued to have no
detectable virus in their blood at the end of 12 additional weeks of follow-on
peg-IFN and RBV dosing. On April 29, 2006, at the 41st Annual Meeting of the
European Association for the Study of the Liver (EASL), Vertex presented
initial results for a 14-day, Phase Ib study of VX-950 and peg-IFN, which
showed that at day 14, the majority of patients (6 of 8) receiving the
combination had HCV RNA levels below the limit of quantitation (30 IU/mL), and
4 of 8 patients had HCV RNA levels below the limit of detection (10 IU/mL).
Researchers reported for the first time at EASL that 8 of 8 patients who
received VX-950 and peg-IFN in combination for 14 days had no detectable virus
in their blood at the end of 12 additional weeks of peg-IFN and RBV dosing.
About Hepatitis C
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 hepatitis C may not experience symptoms, others may have symptoms such as
jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly
increases a person's risk for developing long-term infection, chronic liver
disease, cirrhosis or death. The burden of liver disease associated with HCV
infection is increasing, and current therapies provide sustained benefit in
only about 50% of patients with genotype 1 HCV, the most common strain of the
virus.
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, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of
companies.
TaqMan(R) is a registered trademark of Hoffman-La Roche Inc.
Safe Harbor Statement
This press release may contain forward-looking statements, including
statements that (i) Vertex expects to have the first clinical data from the
PROVE 1 study as early as the fall of 2006; (ii) planned studies will build
extensive clinical activity and safety experience with VX-950 among clinicians
and patients; (iii) the PROVE 1 study will begin dosing patients in June; (iv)
the PROVE 2 study will be initiated in June; (v) Vertex will initiate later in
2006 a Phase II study of VX-950 in approximately 400 patients who have failed
prior HCV therapy; and (vi) by the end of the first quarter of 2007 Vertex
expects to have enrolled approximately 1,000 patients in clinical trials of
VX-950. 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
clinical trials for VX-950 may not proceed as planned due to technical,
scientific, or patient enrollment issues, or disagreements with regulatory
authorities over trial design or other matters, that the scale and scope of
future clinical and nonclinical studies may change and will be determined in
significant part by data collected in ongoing and future trials, that further
clinical studies of VX-950 may not reflect the results obtained in early
clinical and nonclinical studies, that ongoing nonclinical studies, including
toxicology studies, will yield currently unanticipated negative outcomes that
could adversely affect planned clinical trials, that results from the
Company's clinical trials commenced during 2006 will be insufficient to
support a Phase III program without additional trials and consequent delay in
the timetable for potential approval, and other risks listed under Risk
Factors in Vertex's form 10-K filed with the Securities and Exchange
Commission on March 16, 2006.
Conference Call and Webcast: PROVE Study Update
Vertex Pharmaceuticals will host a conference call today, May 23, 2006 at
9:00 a.m. EDT to review the VX-950 global Phase II program. This call will be
broadcast via the Internet at http://www.vrtx.com in the investor center.
Alternatively, to listen to the call on the telephone, dial (800) 374-0296
(U.S. and Canada) or (706) 634-2224 (International). Alternatively, Vertex is
providing a podcast MP3 file available for download on the Vertex website,
http://www.vrtx.com.
The call will be available for replay via telephone commencing May 23,
2006 at 12:00 p.m. EDT running through 5:00 p.m. EDT on May 30, 2006. The
replay phone number for the US and Canada is (800) 642-1687. The
international replay number is (706) 645-9291 and the conference ID number is
9742527. Following the live webcast, an archived version will be available on
Vertex's website until 5:00 p.m. EDT on June 6, 2006.
Vertex Contacts:
Lynne Brum, Vice President, Strategic Communications, (617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Lora Pike, Manager, Investor Relations, (617) 444-6755
Zachry Barber, Senior Media Relations Specialist, (617) 444-6470
/Company News On-Call: http://www.prnewswire.com/comp/938395.html/
/Web site: http://www.vrtx.com/
