-Study in people who have two copies of the
F508del mutation demonstrated a mean absolute improvement in ppFEV1
of 4.0 percentage points compared to placebo (p<0.0001)-
-Study in people who have one mutation that
results in residual CFTR function and one F508del mutation
demonstrated a mean absolute improvement in ppFEV1 of 6.8
percentage points with the tezacaftor/ivacaftor combination
treatment compared to placebo (p<0.0001)-
-Across both studies, the combination treatment
was generally well tolerated-
-Vertex to host investor conference call
tomorrow at 8:00 a.m. EDT-
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced results from two Phase 3 studies of the tezacaftor
(VX-661) / ivacaftor combination treatment that showed
statistically significant improvements in lung function (percent
predicted forced expiratory volume in one second, or ppFEV1) in
people with cystic fibrosis (CF) ages 12 and older who have certain
mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene. The 24-week EVOLVE study evaluated the
combination treatment in people who have two copies of the F508del
mutation. This study met its primary endpoint with a mean absolute
improvement in ppFEV1 through 24 weeks of 4.0 percentage points
from baseline compared to placebo (p<0.0001). The second study,
EXPAND, was an 8-week crossover study that evaluated the
combination treatment in people who have one mutation that results
in residual CFTR function and one F508del mutation. This study met
the primary endpoints of absolute change in ppFEV1 from baseline to
the average of the Week 4 and Week 8 measurements, with the
tezacaftor/ivacaftor combination treatment 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). Based on these results, Vertex plans to
submit 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) in the third quarter
of 2017 for the tezacaftor/ivacaftor combination treatment in
people with CF ages 12 and older who have two copies of the F508del
mutation and in people who have one mutation that results in
residual CFTR function and F508del mutation. Vertex will host a
conference call for investors tomorrow, March 28, 2017 at 8:00 a.m.
EDT, to discuss these results.
Across both studies, the tezacaftor/ivacaftor combination
treatment was generally well tolerated. The most common adverse
events, regardless of treatment group, were infective pulmonary
exacerbation and cough. In both studies, rates of discontinuations
due to adverse events were low and similar between placebo and
treatment groups (2.1% for placebo vs 1.7% for the
tezacaftor/ivacaftor combination). Rates of respiratory adverse
events were similar between placebo and treatment groups (15.0% for
placebo vs 11.4% for the tezacaftor/ivacaftor combination).
“The tezacaftor/ivacaftor combination treatment demonstrated
clinically meaningful benefits, with a favorable safety profile,
across multiple patient groups,” said Jeffrey Chodakewitz, M.D.,
Executive Vice President and Chief Medical Officer at Vertex. “This
combination treatment may provide a promising new option for
treating the underlying cause of CF in the future and brings us
increasingly closer to our goal of developing new medicines for all
people with the disease.”
About the EVOLVE Study:
EVOLVE was a global Phase 3, randomized, double-blind,
placebo-controlled study designed to evaluate the efficacy and
safety of tezacaftor/ivacaftor combination treatment in people with
CF ages 12 and older who have two copies of the F508del mutation.
The combination group received tezacaftor 100 mg once daily (QD) in
combination with ivacaftor 150 mg every 12 hours (q12h). In the
study, more than 500 people were treated at more than 90 trial
sites in North America and Europe. The primary endpoint was
absolute change in ppFEV1 from baseline through Week 24 for those
treated with the tezacaftor/ivacaftor combination treatment
compared to placebo. The mean ppFEV1 at baseline was approximately
60 percent for each study arm. Of the 477 people who completed the
24-week study, 461 chose to enroll in a rollover study to receive
the combination treatment.
Efficacy Results
Primary Endpoint: Through 24 weeks of the study, the mean
absolute improvement in ppFEV1 was 4.0 percentage points from
baseline for those treated with the tezacaftor/ivacaftor
combination compared to placebo (p<0.0001).
Detailed data for the primary endpoint in the study are provided
below:
Mean Absolute Change in ppFEV1 (percentage
points) Placebo
(n=256)
Tezacaftor + Ivacaftor
(n=248)
Treatment Difference N/A
+4.0 (p<0.0001)
Within Group
-0.6 (p=0.0601) +3.4 (p<0.0001)
Key Secondary Endpoints: Statistically significant improvements
were seen in multiple key secondary endpoints, including a 35
percent reduction in the annualized rate of pulmonary exacerbations
with the tezacaftor/ivacaftor combination treatment compared to
placebo.
Detailed data for key secondary endpoints in the study are
provided below:
Key Secondary Endpoints* Placebo
(n=256)
Tezacaftor + Ivacaftor
(n=248)
Mean Relative Change in ppFEV1 (%) Through 24
Weeks Treatment Difference
N/A +6.8 (p<0.0001∧)
Within Group -0.5
(p=0.3823) +6.3 (p<0.0001)
Number of
Pulmonary Exacerbations Through Week 24
Number of Events (rate per 48 weeks)
122 (0.99) 78 (0.64)
Rate Ratio N/A
0.65 (p=0.0054∧)
Change in Body Mass Index at Week 24
Treatment Difference N/A
+0.06 (p=0.4127)
Within Group +0.12 (p=0.0134)
+0.18 (p=0.0004)
Change in CFQ-R Through Week
24 Treatment Difference
N/A +5.1 (p<0.0001)
Within Group -0.1
(p=0.8889) +5.0 (p<0.0001) *A hierarchical
testing procedure was performed for the primary and key secondary
endpoints versus placebo, noted strictly in the order above;
p≤0.050 required for statistical significance
∧Statistical significance was confirmed in
the hierarchical testing procedure
Safety Results
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.
Selected safety data from the study are provided below:
Safety Data Placebo
(n=258)
Tezacaftor + Ivacaftor
(n=251)
Number of Patients who Experienced Any Adverse Event
245 (95.0%) 227 (90.4%)
Number of Patients who Experienced a Serious Adverse Event
47 (18.2%) 31 (12.4%)
Number of Patients who Discontinued Treatment Due To Adverse
Events 8 (3.1%) 7
(2.8%)
Respiratory Adverse Events* 41
(15.9%) 33 (13.1%) * Respiratory events
included dyspnea, respiration abnormal, bronchospasm and other
(wheezing, asthma, chest discomfort, and bronchial
hyper-reactivity)
About the EXPAND Study:
EXPAND was a global Phase 3, randomized, double-blind,
placebo-controlled, crossover, multicenter study designed to
evaluate the efficacy and safety of tezacaftor/ivacaftor
combination treatment as well as ivacaftor monotherapy in people
with CF ages 12 and older who have one mutation that results in
residual CFTR function and one copy of the F508del mutation.
Patients were randomized to one of six treatment groups to receive
tezacaftor/ivacaftor, ivacaftor monotherapy or placebo for eight
weeks, followed by an 8-week washout period. Following the washout
period, patients switched to one of the other two treatment
regimens for another eight weeks. The combination treatment group
evaluated tezacaftor 100 mg once daily (QD) in combination with
ivacaftor 150 mg every 12 hours (q12h), and the monotherapy group
evaluated ivacaftor 150 mg every 12 hours (q12h). In the study,
approximately 250 people were treated at more than 80 trial sites,
mainly in North America and Europe. The primary endpoints were
absolute change in ppFEV1 from baseline to the average of the Week
4 and Week 8 measurements for each of the treatment groups
(tezacaftor/ivacaftor combination treatment and ivacaftor
monotherapy) compared to placebo. The mean ppFEV1 at baseline was
approximately 62 percent for each study arm. Of the 235 people who
completed the study, 227 chose to enroll in a rollover study to
receive tezacaftor/ivacaftor combination treatment.
Efficacy Results
Lung Function: The mean absolute improvement in ppFEV1 was 6.8
percentage points from baseline compared to placebo (p<0.0001)
for those receiving the tezacaftor/ivacaftor combination and was
4.7 percentage points compared to placebo (p<0.0001) for those
receiving ivacaftor alone. An additional pre-specified analysis of
the combination group compared to the monotherapy group showed that
the tezacaftor/ivacaftor combination treatment provided a
statistically significant improvement in ppFEV1 over the use of
ivacaftor alone (2.1 percentage points, p<0.0001).
CFQ-R: The key secondary endpoint was absolute change in the
Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain
score from baseline to the average of the Week 4 and Week 8
measurements for each of the treatment groups (tezacaftor/ivacaftor
combination treatment and ivacaftor monotherapy) compared to
placebo.
Detailed data from the study are provided below:
Primary and Key Secondary Endpoints
Placebo
(n=161)
Treatment Arm Primary Endpoint: Mean
Absolute Change in ppFEV1 (percentage points)
Tezacaftor + Ivacaftor
(n=161)
Treatment Difference
N/A +6.8 (p<0.0001)
Within Group -0.3 (p=0.5035)
+6.5 (p<0.0001)
Ivacaftor
(n=156)
Treatment Difference
N/A +4.7 (p<0.0001)
Within Group -0.3 (p=0.5035)
+4.4 (p<0.0001)
Key Secondary Endpoint:
Mean Absolute Change in CFQ-R Tezacaftor + Ivacaftor
(n=161)
Treatment Difference
N/A +11.1 (p<0.0001)
Within Group -1.0 (p=0.3265)
+10.1 (p<0.0001)
Ivacaftor
(n=156)
Treatment Difference
N/A +9.7 (p<0.0001)
Within Group -1.0 (p=0.3265)
+8.7 (p<0.0001)
Safety Results
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. The tezacaftor/ivacaftor
combination treatment as well as 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.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR
KALYDECO® (ivacaftor)
KALYDECO® (ivacaftor) is a prescription medicine used for the
treatment of cystic fibrosis (CF) in patients age 2 years and older
who have one of the following mutations in their CF gene: G551D,
G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or
R117H. KALYDECO is not for use in people with CF due to other
mutations in the CF gene. KALYDECO is not effective in patients
with CF with two copies of the F508del mutation (F508del/F508del)
in the CF gene. 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 (ivacaftor).
About CF
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 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 protein 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, we believe 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 one mutation that results in residual CFTR
function and one copy of the F508del mutation.
About Vertex
Vertex is a global biotechnology company that aims to discover,
develop and commercialize innovative medicines so people with
serious diseases can lead better lives. In addition to our clinical
development programs focused on cystic fibrosis, Vertex has more
than a dozen ongoing research programs aimed at other serious and
life-threatening diseases.
Founded in 1989 in Cambridge, Mass., Vertex today has research
and development sites and commercial offices in the United States,
Europe, Canada and Australia. For seven years in a row, Science
magazine has named Vertex one of its Top Employers in the life
sciences. 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) and tezacaftor 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, Dr. Chodakewitz’s statements in the
third paragraph, and the information provided regarding Vertex's
plans to submit regulatory applications for tezacaftor/ivacaftor
combination treatment, including a New Drug Application (NDA) in
the United States and Marketing Authorization Application (MAA) in
Europe, in the third quarter of 2017. While Vertex believes the
forward-looking statements contained in this press release are
accurate, these forward-looking statements represent the company's
beliefs only as of the date of this press release, and 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
submitting regulatory filings, that regulatory authorities may not
approve, or approve on a timely basis, tezacaftor/ivacaftor
combination treatment due to safety, efficacy or other reasons, and
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.
Conference Call and
WebcastThe company will host a conference call and
webcast tomorrow at 8:00 a.m. EDT to discuss these results. To
access the call, please dial (866) 501-1537 (U.S.) or +1 (720)
545-0001 (International). The conference call will be webcast live,
and a link to the webcast may be accessed through Vertex's website
at www.vrtx.com in the “Investors” section under “Events and
Presentations.” To ensure a timely connection, it is recommended
that users register at least 10 minutes prior to the scheduled
webcast. An archived webcast will be available on the company's
website.
(VRTX-GEN)
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Vertex Pharmaceuticals
IncorporatedInvestors:Michael Partridge, +1 617 341
6108orEric Rojas, +1 617 961 7205orZach Barber, +1 617 341
6470orMedia:mediainfo@vrtx.comNorth America: +1 617 341
6992orEurope & Australia: +44 20 3204 5275
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