-Marketing Authorization Application (MAA)
variation in Europe planned for third quarter of 2014-
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced the submission of a supplemental New Drug Application
(sNDA) to the U.S. Food and Drug Administration (FDA) for the
approval of KALYDECO® in people with cystic fibrosis (CF) ages 18
and older who have the R117H mutation in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene. In the United
States, KALYDECO is currently approved for use in people with CF
ages 6 and older who have one of the following nine mutations:
G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or
G1349D. CF is caused by a defective or missing CFTR protein that
results from mutations in the CFTR gene. In the United States,
approximately 300 people have the R117H mutation and are 18 years
of age or older. R117H is the most common residual function
mutation and also has a defect in the gating of the CFTR
protein.
“This submission is another step forward in our goal to help
more people with this devastating disease," said Jeffrey
Chodakewitz, M.D., Senior Vice President and Chief Medical Officer
at Vertex. “While people with the R117H mutation exhibit a wide
range in the severity of their disease, their lung function often
declines as they get older, marking the need for new
medicines.”
In addition to the sNDA submission, Vertex intends to submit a
Marketing Authorization Application (MAA) variation
in Europe in the third quarter of 2014 for people
with CF ages 18 and older who have the R117H mutation in the CFTR
gene.
The sNDA submission is based on previously announced data from a
Phase 3 study of ivacaftor that enrolled 69 people with CF ages 6
and older who had at least one R117H mutation. The study did not
meet its primary endpoint of the mean absolute change from baseline
in ppFEV1 (percent predicted forced expiratory volume in one
second) for ivacaftor compared to placebo (treatment difference)
across all patients, however a pre-specified subset analysis in
people who were 18 years of age and older showed statistically
significant improvements in lung function (ppFEV1) and other key
secondary endpoints.
The subset analysis included 50 people with CF ages 18 and older
who had a mean baseline absolute FEV1 of 65 percent predicted.
In these patients, a statistically significant mean absolute
treatment difference of 5.0 percentage points (p=0.01) in ppFEV1
was observed through 24 weeks of treatment, which corresponded to a
mean relative treatment difference of 9.1 percent (p=0.008). Four
weeks following the completion of treatment with ivacaftor,
patients in this subset analysis showed a mean absolute
within-group decrease of -3.1 percentage points (p=0.001) in
ppFEV1. People who took part in this study were eligible to enroll
in an open-label rollover study where all patients received
ivacaftor after a washout period of at least three weeks. After the
first 12 weeks of treatment in the rollover study, the mean
absolute improvement from baseline in lung function for patients
ages 18 and older (n=46) was 5.1 percentage points (p<0.0001).
Across the 24-week study and through 12 weeks of treatment in the
rollover study, treatment with ivacaftor also resulted in decreases
in sweat chloride and improvements in CFQ-R.
Across all the patients, the safety and tolerability results
observed in the 24-week study and rollover study were consistent
with those observed in prior Phase 3 studies of ivacaftor in people
with CF. In the 24-week study, the most commonly observed adverse
events in those who received ivacaftor were infective pulmonary
exacerbation, cough and headache, which occurred with similar
frequency compared to those who received placebo. Serious adverse
events occurred in 17 percent of patients who received placebo
versus 12 percent of patients who received ivacaftor. In the
rollover study, the most common serious adverse event was infective
pulmonary exacerbations.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO™
(ivacaftor)
Ivacaftor (150 mg tablets) is indicated for the treatment of
cystic fibrosis (CF) in patients age 6 years and older who have a
G551D mutation in the CFTR gene.
In the United States, ivacaftor is also indicated for the
treatment of CF in patients age 6 and older who have one of the
following mutations in the CFTR gene: G1244E, G1349D, G178R, G551S,
S1251N, S1255P, S549N, or S549R. In Canada, ivacaftor is indicated
for these same mutations and additionally for G970R.
Ivacaftor is not effective in patients with CF with 2 copies of
the F508del mutation (F508del/F508del) in the CFTR gene.
The safety and efficacy of ivacaftor in children with CF younger
than 6 years of age have not been established.
Elevated liver enzymes (transaminases; ALT and AST) have been
reported in patients receiving ivacaftor. It is recommended that
ALT and AST be assessed prior to initiating ivacaftor, every 3
months during the first year of treatment, and annually thereafter.
Patients who develop increased transaminase levels should be
closely monitored until the abnormalities resolve. Dosing should be
interrupted in patients with ALT or AST of greater than 5 times the
upper limit of normal. Following resolution of transaminase
elevations, consider the benefits and risks of resuming ivacaftor
dosing.
Use of ivacaftor with medicines that are strong CYP3A inducers,
such as the antibiotics rifampin and rifabutin; seizure medications
(phenobarbital, carbamazepine, or phenytoin); and the herbal
supplement St. John's Wort, substantially decreases exposure of
ivacaftor and may diminish effectiveness. Therefore,
co-administration is not recommended.
The dose of ivacaftor must be adjusted when used concomitantly
with strong and moderate CYP3A inhibitors or when used in patients
with moderate or severe hepatic disease.
Ivacaftor can cause serious adverse reactions including
abdominal pain and high liver enzymes in the blood. The most common
side effects associated with ivacaftor include headache; upper
respiratory tract infection (the common cold), including sore
throat, nasal or sinus congestion, and runny nose; stomach
(abdominal) pain; diarrhea; rash; and dizziness. These are not all
the possible side effects of ivacaftor. A list of the adverse
reactions can be found in the product labeling for each country
where ivacaftor is approved. Patients should tell their healthcare
providers about any side effect that bothers them or does not go
away.
Please see KALYDECO U.S. Prescribing Information, EU Summary of
Product Characteristics, Canadian Product Monograph, Australian
Consumer Medicine Information and Product Information, Swiss
Prescribing Information and Patient Information, and the New
Zealand Datasheet and Consumer Medicine Information.
About KALYDECOTM (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 that aims to help the CFTR protein function more normally
once it reaches the cell surface, to help hydrate and clear mucus
from the airways. KALYDECO (150mg, q12h) was first approved by the
U.S. Food and Drug Administration in January 2012 for use in people
with CF ages 6 and older who have at least one copy of the G551D
mutation and in February 2014 for use in people with CF ages 6 and
older who have the following additional CFTR mutations: G178R,
S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In Canada,
KALYDECO was first approved in November 2012 for use in people with
CF ages 6 and older who have at least one copy of the G551D
mutation and in June 2014 for use in people with CF ages 6 and
older who have the following additional CFTR mutations: G178R,
S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D and G970R.
KALYDECO was approved by the European Medicines Agency in July
2012, by the Therapeutic Goods Administration in Australia in July
2013, by Medsafe in New Zealand in December 2013 and by Swissmedic
in Switzerland in January 2014 for use in people with CF ages 6 and
older who have at least one copy of the G551D mutation in the CFTR
gene.
Vertex retains worldwide rights to develop and commercialize
KALYDECO.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening genetic disease
affecting approximately 75,000 people in North
America, Europe and Australia. Today, the median
predicted age of survival for a person with CF is between 34 and 47
years, but the median age of death remains in the mid-20s.
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 more than 1,900 known mutations in
the CFTR gene. Some of these mutations, which can be
determined by a genetic, 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 proteins in people with CF
results in poor flow of salt and water into and out of the cell 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.
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 Vertex's CFTR modulators.
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 four 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.
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
second paragraph of this press release and statements regarding
Vertex's plan to submit a Marketing Authorization Application (MAA)
variation in Europe in the third quarter of 2014. 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 submitting regulatory filings, that
regulatory authorities may not approve, or approve on a timely
basis, ivacaftor for people with the R117H mutation 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 IncorporatedInvestors:Michael Partridge,
617-341-6108orKelly Lewis, 617-961-7530orMedia:Zach Barber,
617-341-6992mediainfo@vrtx.com
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