Published: November 02, 2011
New England Journal of Medicine Publishes Data from Phase 3 STRIVE Study of KALYDECOTM (ivacaftor) in People Ages 12 and Older with a Specific Type of Cystic Fibrosis
CAMBRIDGE, Mass. - (BUSINESS WIRE) - Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) today announced that
the New England Journal of Medicine (NEJM) published data
from a Phase 3 study of KALYDECO (ivacaftor, VX-770), a medicine in
development that targets the defective protein that causes cystic
fibrosis (CF). In this study, called STRIVE, people with CF ages 12 and
older with at least one copy of the G551D mutation who were treated with
KALYDECO (kuh-LYE-deh-koh) experienced significant improvements in lung
function and other measures of disease. Improvements in lung function
(forced expiratory volume in one second, FEV1) were seen as
early as week two and were sustained throughout the 48-week study. The
most commonly reported adverse events were respiratory in nature and
comparable across treatment groups. Data from STRIVE will be published
along with an accompanying editorial in the November 3, 2011 issue of NEJM.
Data from a second pivotal Phase 3 study, ENVISION, which evaluated
KALYDECO in children with CF ages 6 to 11 years who had at least one
copy of the G551D mutation, will be presented at the North American CF
Conference, November 3-5, 2011 in Anaheim, Calif.
"I've been involved in cystic fibrosis care and research for 30 years
and have seen great progress in managing CF symptoms," said Bonnie
Ramsey, M.D., lead author of the STRIVE study and Associate Director of
the Cystic Fibrosis Clinic at Seattle Children's Hospital. "These data
are historic because they are the first to show that targeting the
underlying cause of the disease can improve outcomes for patients."
The results from STRIVE showed a mean absolute improvement in lung
function of 10.6 percentage points through week 24 (primary study
endpoint) among those treated with KALYDECO compared to placebo. The
changes in lung function through week 24 represented a 16.7 percent
relative mean improvement in lung function from baseline compared to
placebo. Through week 48, the mean absolute improvement in lung function
for those treated with KALYDECO was 10.5 percentage points compared to
placebo and the relative mean improvement was 16.9 percent from baseline
compared to placebo. Phase 3 results and product labeling for currently
available CF medicines generally describe relative improvements in lung
function. Adverse events that occurred more frequently among those
treated with KALYDECO compared to placebo were headache, upper
respiratory tract infections, nasal congestion, rash, dizziness and
bacteria in the sputum. Events that were more common among those in the
placebo group than in the KALYDECO group were pulmonary exacerbation,
cough, hemoptysis (bloody cough) and decreased pulmonary function.
"The discovery of the CF gene more than two decades ago gave us hope
that we'd one day be able to develop medicines that would treat more
than just the symptoms of this disease," said Peter Mueller, Ph.D.,
Chief Scientific Officer and Executive Vice President of Global Research
and Development at Vertex. "We now have a potential new medicine that
targets the cause of the disease and has shown an ability to help some
people with CF breathe better."
"KALYDECO represents an entirely new approach to treating CF and
provides exciting evidence of the progress that has been made in the
fight against the disease," said Robert J. Beall, Ph.D., President and
CEO of the CF Foundation.
CF is a life-threatening genetic disease that is caused by defective or
missing cystic fibrosis transmembrane conductance regulator (CFTR)
proteins resulting from mutations in the CFTR gene. The absence
of functional CFTR proteins results in poor flow of salt and water
across cell membranes in a number of organs, including the lungs. This
leads to the buildup of abnormally thick, sticky mucus that can cause
chronic lung infections and progressive lung damage. Currently available
medicines have led to improved treatment and outcomes for people living
with CF by treating the symptoms and some of the complications of the
disease.
In some people, CFTR proteins are present at the cell surface but do not
function properly. This dysfunction is known as a gating defect, the
most common of which is the G551D mutation. Approximately 4 percent of
those with CF, or about 1,200 people in the United States and 1,000
people in Europe, are believed to have the G551D mutation. KALYDECO is
designed to keep the CFTR channels at the cell surface open longer to
improve the transport of chloride ions across the cell membrane in
people who have gating mutations. If approved, KALYDECO will be first
treatment to target the underlying cause of CF.
In October 2011, Vertex submitted a New Drug Application (NDA) to the
U.S. Food and Drug Administration (FDA) and a marketing authorization
application (MAA) to the European Medicines Agency (EMA) for KALYDECO,
Vertex's CFTR potentiator. Vertex requested Priority Review from the FDA
and has received agreement from the EMA for accelerated assessment of
KALYDECO in Europe.
Summary of Key Data from STRIVE
Improvements across all key disease measures, including lung function,
respiratory symptoms and weight gain were demonstrated among patients
treated with KALYDECO compared to those who received placebo in the
STRIVE study. There also was a reduction in pulmonary exacerbations
among people who were treated with KALYDECO.
Lung Function: Progressive lung disease is a major source of
illness and is the leading cause of death in people with CF. The primary
endpoint of STRIVE was mean absolute improvement from baseline in lung
function (FEV1) and is reported in the NEJM
publication.
Baseline lung function in STRIVE was 63.5 percent predicted for patients
in the KALYDECO treatment group and 63.7 percent predicted among those
in the placebo control group. Results of the STRIVE study showed that
people treated with KALYDECO experienced rapid, significant and
sustained improvements in lung function throughout the 48 week study.
Sweat Chloride: Elevated sweat chloride levels are a diagnostic
hallmark in CF and are the result of CFTR protein dysfunction. Although
not a clinically validated endpoint, a reduction in sweat chloride is
considered to be a marker of improved CFTR function. The amount of
chloride in the sweat is measured using a standard test. People with CF
typically have elevated sweat chloride levels in excess of 60 mmol/L,
while normal values are less than 40 mmol/L.
In STRIVE, the baseline sweat chloride level for both treatment groups
was approximately 100 mmol/L. People who received KALYDECO experienced a
significant and rapid reduction in the amount of salt in their sweat
(sweat chloride concentration). As early as two weeks after dosing
initiation, patients treated with KALYDECO experienced an average
reduction in sweat chloride of approximately 45 mmol/L. The decreases in
sweat chloride among these patients were maintained through week 48, at
which time the mean sweat chloride level was 50.4 mmol/L. The mean
absolute improvement in sweat chloride for those treated with KALYDECO
was 48.1 mmol/L through week 48, compared to placebo (p <0.0001). Those
treated with the placebo maintained mean baseline sweat chloride levels
of approximately 100 mmol/L through 48 weeks.
Weight: Many people with CF have a hard time gaining and
maintaining weight due to factors such as reduced pulmonary function,
nutrition, chronic infection and inflammation. In STRIVE, people treated
with KALYDECO gained weight throughout the study and by week 48 weighed,
on average, 3.1kg (6.9 lbs) more than at the start of the study. Those
in the placebo group gained 0.4kg (0.9 lbs) by week 48.
Pulmonary Exacerbation: Pulmonary exacerbations are periods of
worsening in signs and symptoms of the disease requiring treatment with
antibiotics. At week 48, 67 percent of those treated with KALYDECO were
free from pulmonary exacerbations, as compared with 41 percent in the
placebo group. In STRIVE, people treated with KALYDECO were 55 percent
less likely to experience a pulmonary exacerbation compared to those
treated with placebo.
Patient-Reported Outcomes: The Cystic Fibrosis Questionnaire -
Revised (CFQ-R) is a validated patient-reported outcome tool that was
used in the STRIVE study to measure the impact of KALYDECO on overall
health, daily life, perceived well-being and symptoms. One aspect of the
CFQ-R, referred to as the respiratory domain, addresses patient reported
symptoms including things such as coughing, congestion, wheezing and
other respiratory symptoms. In STRIVE, statistically significant and
clinically meaningful improvements in respiratory symptoms (a secondary
endpoint of the study) were reported among those treated with KALYDECO,
as compared to those receiving placebo.
Safety: The incidence of adverse events through week 48 was
similar between groups. Adverse events that occurred more frequently
among those treated with KALYDECO compared to placebo were headache,
upper respiratory tract infections, nasal congestion, rash, dizziness
and bacteria in the sputum; none of which were considered serious or led
to discontinuation. The most commonly reported serious adverse events
included pulmonary exacerbation (13 percent in the KALYDECO group
compared to 33 percent in the placebo group), hemoptysis (or bloody
cough; 1 percent in the KALYDECO group and 5 percent in the placebo
group) and hypoglycemia (2 percent in the KALYDECO group and zero in the
placebo group). Discontinuations through 48 weeks due to adverse events
were less frequent in the KALYDECO treatment group compared to placebo
(1 percent compared to 3.8 percent).
About STRIVE
STRIVE evaluated 161 patients 12 years or older who received at least
one dose of either KALYDECO as a single 150 mg tablet (n=83) or placebo
(n=78) twice daily. The study was designed to evaluate KALYDECO in
people with at least one copy of the G551D CFTR mutation. The primary
endpoint of the study was mean absolute change from baseline in
predicted FEV1 (lung function) through week 24. Lung function
was assessed using a standard test that measures the amount of air a
person can exhale in one second (forced expiratory volume in one second,
or FEV1).
About KALYDECO
KALYDECO (ivacaftor, VX-770) is Vertex's lead medicine in development
for the treatment of people with cystic fibrosis who have the G551D CFTR
mutation. Known as a CFTR potentiator, KALYDECO is an oral medicine that
aims to help CFTR protein function more normally once it reaches the
cell surface, to help hydrate and clear mucus from the airways. Vertex
retains worldwide rights to develop and commercialize KALYDECO. The
brand name KALYDECO has been approved by the EMA and provisionally
approved by the FDA for use in connection with VX-770, but VX-770 itself
has not received marketing authorization or NDA approval from any
regulatory authorities.
Expanded Access Programs for KALYDECO
An expanded access program for KALYDECO is currently open at
participating clinical trial sites in the United States. This program is
designed to provide KALYDECO to people ages 6 and older who have at
least one copy of the G551D mutation, are in critical medical need and
may benefit from treatment prior to potential FDA approval in the United
States.
Vertex is working toward implementing additional expanded access
programs in other countries, with a goal of opening programs for
eligible patients by the end of 2011.
For more information, please call Vertex Medical Information at
1-877-634-VRTX (8789).
About Cystic Fibrosis
CF is a life-threatening genetic disease affecting approximately 30,000
people in the United States and 70,000 people worldwide. Today, the
median predicted age of survival for a person with CF is approximately
38 years. According to the 2010 Cystic Fibrosis Foundation Patient
Registry Annual Data Report, approximately 4 percent of the total CF
patient population in the United States have at least one copy of the
G551D mutation.
Collaborative History with Cystic Fibrosis Foundation Therapeutics,
Inc. (CFFT)
Vertex initiated its CF research program in 1998 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. This collaboration was
expanded to support the accelerated discovery and development of
KALYDECO and other CFTR modulators.
About the Cystic Fibrosis Foundation
The Cystic Fibrosis Foundation is the world's leader in the search for a
cure for cystic fibrosis. The Foundation funds more CF research than any
other organization and nearly every CF drug available today was made
possible because of Foundation support. Based in Bethesda, Md., the
Foundation also supports and accredits a national care center network
that has been recognized by the National Institutes of Health as a model
of care for a chronic disease. The CF Foundation is a donor-supported
nonprofit organization. For more information, visit www.cff.org.
About Vertex
Vertex creates new possibilities in medicine. Our team discovers,
develops and commercializes innovative therapies so people with serious
diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to
cure or significantly advance the treatment of hepatitis C, cystic
fibrosis, rheumatoid arthritis, epilepsy and other life-threatening
diseases.
Founded more than 20 years ago in Cambridge, Mass., we now have ongoing
worldwide research programs and sites in the U.S., U.K. and Canada.
Today, Vertex has more than 1,900 employees around the world, and Science
magazine named Vertex number one on its 2011 list of Top Employers in
the life sciences.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements, as defined in
the Private Securities Litigation Reform Act of 1995, as amended,
including statements regarding (i) Vertex's potential new medicine that
targets the cause of the disease and has demonstrated the ability to
help patients breathe better; (ii) the potential that KALYDECO will be
approved; and (iii) the possibility that additional expanded access
programs will be implemented with the goal of opening programs to
eligible patients by the end of 2011. 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 Vertex could experience unforeseen delays in obtaining approval to
market KALYDECO; that future outcomes from clinical trials of KALYDECO
may not be favorable; that future scientific, clinical, competitive or
other market factors may adversely affect the potential for KALYDECO and
the other risks listed under Risk Factors in Vertex's annual report and
quarterly reports filed with the Securities and Exchange Commission and
available through Vertex's website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.
(VRTX-GEN)
Vertex Pharmaceuticals Incorporated
Media:
617-444-6992
or mediainfo@vrtx.com
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Kalmar
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or
Investors:
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Partridge, 617-444-6108
or
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or
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