-Vertex to Advance Clinical Program; Company Expects to Initiate Combination
Study of VX-702 and Methotrexate by Mid-2006-
CAMBRIDGE, Mass., March 8 /PRNewswire-FirstCall/ -- Vertex Pharmaceuticals
Incorporated (Nasdaq: VRTX) today announced that its investigational p38 MAP
kinase inhibitor, VX-702, has met its primary objectives in a 12-week Phase II
clinical study involving 315 patients. A preliminary analysis indicates that
VX-702 was well-tolerated through 12 weeks of dosing, and demonstrated
statistically significant clinical effects on signs and symptoms of rheumatoid
arthritis (RA), as determined by ACR20 criteria, as well as several other
widely used clinical measures. The Company continues to conduct a full
analysis of safety, pharmacokinetics and efficacy data from the study. Vertex
anticipates that results from the study will be presented at a medical
conference later in 2006. The preliminary results from this study support
Vertex's plans to advance its clinical program and to initiate by mid-2006
clinical studies of VX-702 in combination with methotrexate, a commonly used
therapy for RA. VX-702, dosed as one tablet, once a day, is one of the lead
agents in a new class of investigational oral anti-cytokine therapies.
"Demonstration of clear effects on the signs and symptoms of RA, in
conjunction with good tolerability with three months of treatment, represents
a major achievement for the VX-702 clinical program," commented John Alam,
M.D., Executive Vice President, Medicines Development and Chief Medical
Officer at Vertex. "The preliminary data announced today provide strong
support for our plans to move forward in clinical development and evaluate
VX-702 in combination with methotrexate in RA patients."
VeRA: Clinical Study Design and Results
The VeRA study is a randomized, double-blind, 12-week, Phase II clinical
study that enrolled 315 patients with moderate to severe RA. A total of 278
patients completed 12 weeks of treatment. The study was conducted at more
than 40 centers in Eastern and Central Europe. Patients received either 5 mg
or 10 mg VX-702 once daily, or placebo. In addition, patients could receive
certain disease-modifying anti-rheumatic drugs (DMARDs), but could not receive
methotrexate or anti-TNF therapies. At the end of 12 weeks, patients
completed dosing with VX-702 and were evaluated for improvement in clinical
signs and symptoms according to American College of Rheumatology (ACR)
criteria.
Effects on Signs and Symptoms of Rheumatoid Arthritis: VX-702 treatment
led to a dose-dependent, statistically significant increase in week 12 ACR20
response rates, the primary endpoint of the study. Thirty percent of patients
receiving placebo, 38% of those receiving 5 mg VX-702 and 40% of those
receiving 10 mg VX-702 achieved an ACR20 response at week 12 (p=0.04;
Jonckheere-Terpstra test for increasing dose-response). In addition, 32% of
placebo patients, 41% of 5 mg VX-702-treated patients and 44% of 10 mg
VX-702-treated patients achieved a EULAR (moderate or good) response (p=0.01).
Dose-dependent, statistically significant effects were also seen on tender
joint counts (p=0.007), swollen joint counts (p=0.003), disease activity score
(DAS28; p=0.02) and morning stiffness (p=0.03). Analyses of additional
clinical measures and biomarkers are ongoing.
Safety and Tolerability: A preliminary analysis of study data indicates
that VX-702 was well-tolerated. Premature discontinuations for adverse events
were low across the study arms: placebo (2%), 5 mg (3%) and 10 mg (5%). No
clinically significant effects were seen on laboratory parameters, including
liver function tests. The most common adverse events that led to treatment
discontinuation in patients receiving VX-702 were seen in two patients each
and were: gastroenteritis, nausea/vomiting, rash, and renal impairment
(increased serum creatinine levels to 1.2 to 1.5 times upper limit of normal).
Based on preliminary analysis, the most common adverse events were generally
mild or moderate and were: infection (5% of placebo patients and 10% of VX-702
patients), GI disorders (6% placebo and 8% VX-702), and skin disorders (0%
placebo and 9% VX-702).
Extensive ambulatory and 12-lead electrocardiographic monitoring was also
performed on patients throughout the study. No differences in ventricular
ectopic (VE) activity or cardiac arrhythmias were observed between placebo and
treated patients. On digital electrocardiograms, from baseline to end of
treatment, a minimal (average approximately 1.5% or less for each group)
dose-dependent increase in the Fridericia rate-corrected QT interval (QTcF)
was seen in the VX-702 treatment groups. No patient experienced a clinically
significant (60 msec, or approximately 15%) increase in QTcF at any time in
the study.
Clinical Plans
By mid-2006, Vertex expects to initiate clinical studies of VX-702 in
combination with methotrexate, including a three-month, dose-ranging Phase II
study in more than 200 patients at centers in Eastern and Central Europe.
Doses will be determined based on the final analysis of the VeRA study. Also
in 2006, Vertex expects to file an investigational new drug (IND) application
to conduct supporting clinical studies of VX-702 in the United States.
About RA and p38 MAP Kinase
More than 2 million people in the U.S. and 5 million people worldwide
suffer from RA, a chronic disease that causes pain, swelling and stiffness in
the joints of hands, feet and wrists. In RA, the immune system attacks joint
tissue, causing chronic inflammation and irreversible damage to cartilage,
tendons and bones. The long-term prognosis for patients with RA is poor, and
as a result, many patients face increased disability and premature death.
P38 MAP kinase inhibitors have the potential to be a powerful new class of
oral anti-inflammatory medicines that reduce cytokine activity through a novel
mechanism of action. P38 MAP kinase regulates the production of the
inflammatory cytokines TNF-alpha, interleukin-1 (IL-1) beta, and IL-6, which
have been implicated in a range of inflammatory diseases including RA. Vertex
holds development and commercial rights in the United States and Europe for
its p38 MAP kinase inhibitors. Kissei Pharmaceutical Co., Ltd. holds
development and commercial rights in Japan and certain Asian countries for
VX-702. In 2005, Kissei initiated clinical development of VX-702 in Japan.
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.
Safe Harbor Statement
This press release may contain forward-looking statements, including
statements that (i) VX-702 is one of the lead agents in a new class of
investigational oral anti-cytokine therapies; (ii) Vertex expects to advance
its VX-702 clinical program and to initiate clinical studies of VX-702 in
combination with methotrexate by mid-2006; (iii) in mid-2006, Vertex expects
to initiate a three-month, dose-ranging study in more than 200 patients in
Eastern and Central Europe; and (iv) in 2006, Vertex expects to file an
investigational new drug (IND) application to conduct supporting clinical
studies of VX-702 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 full analysis of the data, including an ongoing
detailed safety analysis, or further testing, will not reflect the interim
results reported in this press release, or support any or all of the
conclusions provided in this press release; clinical trials for VX-702 may not
proceed as planned due to technical, scientific, or patient enrollment issues;
expected regulatory filings or clinical trial starts may not occur or may be
delayed due to adverse clinical or non-clinical trial developments or FDA
action; and other risks listed under Risk Factors in Vertex's Form 10-K filed
with the Securities and Exchange Commission on March 16, 2005.
Lexiva is a registered trademark of the GlaxoSmithKline group of
companies.
Vertex's press releases are available at http://www.vrtx.com.
Vertex Contacts:
Lynne H. 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
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 H. Brum, Vice President, Strategic
Communications, +1-617-444-6614, Michael Partridge, Director,
Corporate Communications, +1-617-444-6108, Lora Pike, Manager,
Investor Relations, +1-617-444-6755, or Zachry Barber, Senior
Media Relations Specialist, +1-617-444-6470, all of Vertex
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