- Data showed significant improvements in lung
function (ppFEV1) with a favorable safety profile across multiple
patient groups -
- Tezacaftor/ivacaftor currently under review
by the FDA and EMA; FDA Priority Review action date of February 28,
2018 -
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced
today that the New England Journal of Medicine (NEJM) published two
articles with results from two Phase 3 studies of the
tezacaftor/ivacaftor combination treatment, a medicine in
development that is designed to treat the underlying cause of
cystic fibrosis (CF) in people ages 12 and older who have certain
mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene. In both studies, the tezacaftor/ivacaftor
combination demonstrated statistically significant and clinically
meaningful improvements in lung function and other measures of
disease. The EVOLVE study evaluated the combination in people who
have two copies of the F508del mutation, the most common mutation
in the CFTR gene. The EXPAND study evaluated the combination in
people with one F508del mutation and one mutation that results in
residual CFTR function. The results were published in two online
articles today in conjunction with two oral presentations at the
31st Annual North American Cystic Fibrosis Conference, November 2
to 4, 2017 in Indianapolis. These data formed the basis of
applications for the approval of the tezacaftor/ivacaftor
combination that are currently under review with regulatory
agencies in the United States and Europe. In the United
States, the Food and Drug Administration (FDA) has
granted Priority Review of the application and has set an action
date of February 28, 2018.
“We have made unprecedented progress in the treatment of CF in
recent years, but we continue to drive ourselves to deliver even
greater benefits for patients today and more new medicines for
patients who are still waiting,” said Jeffrey Chodakewitz, M.D.,
Executive Vice President and Chief Medical Officer at Vertex.
“These tezacaftor/ivacaftor results are exciting because they
represent the potential to do both.”
Summary of Key Data from EVOLVE
The 24-week EVOLVE study evaluated tezacaftor/ivacaftor in more
than 500 people with CF ages 12 and older who have two copies of
the F508del mutation. Improvements across multiple disease
measures, including lung function, were demonstrated among patients
treated with tezacaftor/ivacaftor compared to those who received
placebo. There was also a reduction in pulmonary exacerbations
among those treated with tezacaftor/ivacaftor.
“In this study, the tezacaftor/ivacaftor combination
demonstrated significant, clinically meaningful improvements in
lung function and other measures of cystic fibrosis health status,”
said Jennifer Taylor-Cousar, M.D., co-lead author of the EVOLVE
study and Associate Professor, Departments of Medicine and
Pediatrics, Pulmonary Divisions, Medical Director of Clinical
Research Services and Co-Director and Director of the CF
Therapeutics Development Network, Adult CF Program, National Jewish
Health, Colorado. “Tezacaftor/ivacaftor was also very well
tolerated, which makes it an important potential new option for
helping our patients feel better and change the course of their
disease. The fact that tezacaftor/ivacaftor will be the basis of
triple combination therapy makes this positive data even more
exciting for patients with CF and the physicians who care for
them.”
Lung Function: Progressive lung disease is a major source
of illness and is the leading cause of death in people with CF. The
study met its primary endpoint with a mean absolute improvement in
lung function (measured as percent predicted forced expiratory
volume in one second, or ppFEV1) through 24 weeks of 4.0 percentage
points from baseline compared to placebo (p<0.0001). This
equates to a mean relative improvement (a key second endpoint in
the study), which is an assessment of the percentage change, of 6.8
percent (p<0.0001).
Pulmonary Exacerbations: Pulmonary exacerbations are
episodes of worsening signs and symptoms of the disease that often
require treatment with intravenous antibiotics or hospitalization.
Through the 24-week study, those receiving tezacaftor/ivacaftor had
a 35 percent reduction in the annualized rate of pulmonary
exacerbations compared to those on placebo (p=0.0054). In addition,
patients receiving tezacaftor/ivacaftor were 47 percent less likely
to experience a pulmonary exacerbation that required
hospitalization or intravenous antibiotics than those receiving
placebo (p=0.0042).
Body Mass Index: Body mass index, or BMI, is a measure of
body fat based on a person’s height and weight. For people with CF,
BMI is one way of assessing nutritional status; poor nutritional
status, and thus lower BMI, is associated with worse lung function.
In EVOLVE, people receiving tezacaftor/ivacaftor had a
non-statistically significant BMI increase of 0.06 compared to
those receiving placebo (p=0.4127).
Patient-Reported Outcomes: The Cystic Fibrosis
Questionnaire — Revised (CFQ-R) is a validated patient-reported
outcome tool that was used in the EVOLVE study to measure the
impact of tezacaftor/ivacaftor 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 EVOLVE, the mean absolute
improvement in the respiratory domain of CFQ-R at Week 24 was 5.1
compared to those receiving placebo (p<0.0001). This increase is
considered nominally statistically significant.
Safety: The tezacaftor/ivacaftor combination treatment
was generally well tolerated. The majority of adverse events were
mild or moderate. The most common adverse events (≥15%), regardless
of treatment group, were infective pulmonary exacerbation, cough,
headache, nasopharyngitis and sputum increased. The rate of
discontinuations due to adverse events was low and similar between
the placebo group and the combination treatment group. Rates of
adverse events, serious adverse events and respiratory-related
adverse events were similar between the placebo and the
tezacaftor/ivacaftor combination treatment groups.
Summary of Key Data from EXPAND
The EXPAND study evaluated eight weeks of treatment with the
tezacaftor/ivacaftor combination, ivacaftor monotherapy or placebo
in approximately 250 people with CF ages 12 and older who have one
F508del mutation and one mutation that results in residual CFTR
function. Improvements across multiple disease measures, including
lung function, were demonstrated among patients treated with
tezacaftor/ivacaftor and those treated with ivacaftor alone in the
study compared to those who received placebo.
“This is an exciting time to be part of cystic fibrosis research
as we continue to improve outcomes for patients,” said Steven M.
Rowe, M.D., M.S.P.H., co-lead author of the EXPAND study and
Professor of Medicine, Pediatrics, and Cell, Developmental and
Integrative Biology, Director of the Gregory Fleming James Cystic
Fibrosis Research Center, Nancy and Eugene Gwaltney Endowed Chair
in Medical Research, University of Alabama at Birmingham. “These
results are particularly exciting because they demonstrate that by
addressing the underlying cause of cystic fibrosis, the
tezacaftor/ivacaftor combination offers significant benefits for
many people with this severe and life-shortening disease, while
also offering increased benefit over KALYDECO alone in patients
with residual function mutations.”
Lung Function: The EXPAND study met its primary endpoint
of absolute improvement in lung function, with those receiving
tezacaftor/ivacaftor demonstrating a mean absolute improvement of
6.8 percentage points compared to placebo (p<0.0001) and the
ivacaftor monotherapy group demonstrating a mean absolute
improvement of 4.7 percentage points compared to placebo
(p<0.0001). Improvements in lung function were measured as the
change in ppFEV1 from the start of the study (baseline) to the
average of the Week 4 and Week 8 measurements. An additional
pre-specified analysis showed that the tezacaftor/ivacaftor
combination treatment provided a statistically significant
improvement in ppFEV1 over ivacaftor alone (2.1 percentage points,
p<0.0001).
Patient-Reported Outcomes: In EXPAND, the mean absolute
improvement in the respiratory domain of CFQ-R (the key secondary
endpoint), measured as the average of the Week 4 and Week 8
measurements, was 11.1 for those receiving tezacaftor/ivacaftor and
was 9.7 for those receiving ivacaftor, both compared to placebo
(p<0.0001).
Safety: In the EXPAND study, the safety profile observed
for the tezacaftor/ivacaftor combination treatment was favorable
and similar to that seen in the EVOLVE study. Tezacaftor/ivacaftor
combination treatment and ivacaftor monotherapy were both generally
well tolerated. The majority of adverse events were mild or
moderate. The most common adverse events (≥15%), regardless of
treatment group, were cough and infective pulmonary exacerbation.
There were no discontinuations due to adverse events in the
combination treatment group. Discontinuations due to adverse events
were low and similar between the placebo group and the ivacaftor
monotherapy group. The incidence of adverse events, serious adverse
events and respiratory-related adverse events was similar between
the placebo, tezacaftor/ivacaftor combination and ivacaftor
monotherapy groups.
About Cystic Fibrosis
Cystic Fibrosis (CF) is a rare, life-shortening genetic disease
affecting approximately 75,000 people in North America, Europe and
Australia.
CF is caused by a defective or missing cystic fibrosis
transmembrane conductance regulator (CFTR) protein resulting from
mutations in the CFTR gene. Children must inherit two defective
CFTR genes — one from each parent — to have CF. There are
approximately 2,000 known mutations in the CFTR gene. Some of these
mutations, which can be determined by a genetic test, or genotyping
test, lead to CF by creating non-working or too few CFTR proteins
at the cell surface. The defective function or absence of CFTR
protein results in poor flow of salt and water into and out of the
cell in a number of organs. In the lungs, this leads to the buildup
of abnormally thick, sticky mucus that can cause chronic lung
infections and progressive lung damage in many patients that
eventually leads to death. The median age of death is in the
mid-to-late 20s.
In people with the F508del mutation, the CFTR protein is not
processed, or folded, normally within the cell and generally does
not reach the cell surface. Tezacaftor is designed to address the
processing defect of F508del-CFTR to enable it to reach the cell
surface where ivacaftor can further enhance the protein's
function.
In North America, Europe and Australia, there are more than
22,000 people ages 12 and older who have two copies of the F508del
mutation, and there are more than 1,500 people ages 12 and older
who have at least one residual function mutation that is responsive
to tezacaftor/ivacaftor in vitro or in the clinic.
About KALYDECO® (ivacaftor)
KALYDECO (ivacaftor) is the first medicine to treat the
underlying cause of CF in people with specific mutations in
the CFTR gene. Known as a CFTR potentiator, KALYDECO is
an oral medicine designed to keep CFTR proteins at the cell surface
open longer to improve the transport of salt and water across the
cell membrane, which helps hydrate and clear mucus from the
airways. KALYDECO is available as 150 mg tablets for adults and
pediatric patients age 6 years and older, and is taken with
fat-containing food. It is also available as 50 mg and 75 mg
granules in pediatric patients ages 2 to less than 6 years and is
administered with soft-food or liquid with fat-containing food.
People with CF who have specific mutations in
the CFTR gene are currently benefiting from KALYDECO in
27 different countries across North
America, Europe and Australia.
KALYDECO® (ivacaftor) INDICATION AND
IMPORTANT SAFETY INFORMATION
KALYDECO (ivacaftor) is a prescription medicine used for the
treatment of cystic fibrosis (CF) in patients age 2 years and older
who have at least one mutation in their CF gene that is responsive
to KALYDECO. Patients should talk to their doctor to learn if they
have an indicated CF gene mutation. It is not known if KALYDECO is
safe and effective in children under 2 years of age.
Patients should not take KALYDECO if they are taking certain
medicines or herbal supplements such as: the antibiotics
rifampin or rifabutin; seizure medications such as phenobarbital,
carbamazepine, or phenytoin; or St. John's wort.
Before taking KALYDECO, patients should tell their doctor if
they: have liver or kidney problems; drink grapefruit
juice, or eat grapefruit or Seville oranges; are pregnant
or plan to become pregnant because it is not known if KALYDECO will
harm an unborn baby; and are breastfeeding or planning to
breastfeed because is not known if KALYDECO passes into breast
milk.
KALYDECO may affect the way other medicines work, and other
medicines may affect how KALYDECO works. Therefore the
dose of KALYDECO may need to be adjusted when taken with certain
medications. Patients should especially tell their doctor if they
take antifungal medications such as ketoconazole, itraconazole,
posaconazole, voriconazole, or fluconazole; or antibiotics such as
telithromycin, clarithromycin, or erythromycin.
KALYDECO can cause dizziness in some people who take it.
Patients should not drive a car, use machinery, or do anything that
needs them to be alert until they know how KALYDECO affects them.
Patients should avoid food containing grapefruit
or Seville oranges while taking KALYDECO.
KALYDECO can cause serious side effects including:
High liver enzymes in the blood have been reported in
patients receiving KALYDECO. The patient's doctor will do
blood tests to check their liver before starting KALYDECO, every 3
months during the first year of taking KALYDECO, and every year
while taking KALYDECO. For patients who have had high liver enzymes
in the past, the doctor may do blood tests to check the liver more
often. Patients should call their doctor right away if they have
any of the following symptoms of liver problems: pain or discomfort
in the upper right stomach (abdominal) area; yellowing of their
skin or the white part of their eyes; loss of appetite; nausea or
vomiting; or dark, amber-colored urine.
Abnormality of the eye lens (cataract) has been noted in some
children and adolescents receiving KALYDECO. The patient's doctor
should perform eye examinations prior to and during treatment with
KALYDECO to look for cataracts. The most common side effects
include headache; upper respiratory tract infection (common cold),
which includes sore throat, nasal or sinus congestion, and runny
nose; stomach (abdominal) pain; diarrhea; rash; nausea; and
dizziness.
These are not all the possible side effects of KALYDECO.
Please click here to see the full
Prescribing Information for KALYDECO.
About Vertex
Vertex is a global biotechnology company that invests in
scientific innovation to create transformative medicines for people
with serious and life-threatening diseases. In addition to clinical
development programs in CF, Vertex has more than a dozen ongoing
research programs focused on the underlying mechanisms of other
serious diseases.
Founded in 1989 in Cambridge, Mass., Vertex's headquarters
is now located in Boston's Innovation District. Today,
the company has research and development sites and commercial
offices in the United
States, Europe, Canada and Australia. Vertex is
consistently recognized as one of the industry's top places to
work, including being named to Science magazine's Top
Employers in the life sciences ranking for eight years in a row.
For additional information and the latest updates from the company,
please visit www.vrtx.com.
Collaborative History with Cystic Fibrosis Foundation
Therapeutics, Inc. (CFFT)
Vertex initiated its CF research program in 2000 as part of a
collaboration with CFFT, the nonprofit drug discovery and
development affiliate of the Cystic Fibrosis Foundation.
KALYDECO® (ivacaftor), ORKAMBI®(lumacaftor/ivacaftor),
tezacaftor, VX-440, VX-152 and VX-659 were discovered by Vertex as
part of this collaboration.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995,
including, without limitation, statements in the second, fourth and
eleventh paragraphs and statements regarding the
tezacaftor/ivacaftor combination and the timing of the potential
regulatory approval of the tezacaftor/ivacaftor combination. While
Vertex 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, (i) that regulatory
authorities may not approve, or approve on a timely basis, the
tezacaftor/ivacaftor combination due to safety, efficacy or other
reasons, and (ii) 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. Vertex disclaims any obligation to
update the information contained in this press release as new
information becomes available.
(VRTX-GEN)
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Vertex Pharmaceuticals IncorporatedInvestors:Michael
Partridge, 617-341-6108orEric Rojas, 617-961-7205orZach Barber,
617-341-6470orMedia:mediainfo@vrtx.comorNorth America:Megan
Goulart, + 1-617-341-6992orEurope & Australia:Rebecca
Hunt, +44 7718 962 690
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