-Data from across Vertex’s cystic fibrosis
research and development programs to be presented at the 28th
Annual North American Cystic Fibrosis Conference (NACFC) beginning
today-
-Interim analysis of rollover study following
the Phase 3 TRAFFIC and TRANSPORT studies showed sustained
improvements in lung function through 48 weeks of treatment with
lumacaftor in combination with ivacaftor in people with two copies
of the F508del mutation-
-Phase 3 pivotal program of VX-661 in
combination with ivacaftor planned for the first half of 2015 in
people with 1 or 2 copies of the F508del mutation, pending
regulatory discussions and data from a fully enrolled 12-week Phase
2b study of VX-661 and ivacaftor-
-New Drug Application submitted for approval of
ivacaftor in children ages 2 to 5 with specific mutations in the
CFTR gene-
Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) today reviewed
recent progress and announced upcoming milestones in its efforts to
develop multiple combinations of medicines that treat the
underlying cause of cystic fibrosis (CF) for the majority of people
with the disease. These updates were made in conjunction with the
28th Annual North American Cystic Fibrosis Conference (NACFC),
which begins today in Atlanta. The company will webcast an investor
presentation from the conference at 6:15 p.m. ET on Friday, October
10. The webcast can be accessed live through Vertex’s website.
KALYDECO® (ivacaftor) is currently approved to treat more
than 2,600 people ages 6 and older in North America, Europe and
Australia who have specific mutations in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene. In the United
States, these mutations include G551D, G178R, S549N, S549R, G551S,
G1244E, S1251N, S1255P and G1349D. Cystic fibrosis is caused by a
defective or missing CFTR protein that results from mutations in
the CFTR gene. Multiple clinical studies are complete, underway or
planned that are designed to evaluate whether ivacaftor, used alone
or in combination with other potential CF medicines known as CFTR
correctors, may help more people with CF, including people with one
or two copies of the most common mutation, F508del. Data from
several of these studies will be presented at NACFC, including the
results of the Phase 3 TRAFFIC and TRANSPORT studies of the CFTR
corrector lumacaftor in combination with ivacaftor, as well as the
first interim data from a rollover study of patients who completed
treatment in TRAFFIC and TRANSPORT. Other presentations include
data from Phase 2 and 3 studies of ivacaftor and Phase 2 studies of
VX-661, Vertex’s second CFTR corrector, in combination with
ivacaftor. Additionally, Vertex today announced that it plans to
initiate a pivotal Phase 3 development program for VX-661 in
combination with ivacaftor that will evaluate people with CF who
have one or two copies of the F508del mutation, including people
whose second CFTR mutation is known to cause a defect in the gating
of the CFTR protein, pending regulatory discussions and data from
an ongoing 12-week Phase 2b study of VX-661 in combination with
ivacaftor in people with two copies of the F508del mutation.
“With KALYDECO, we have shown that treating the underlying cause
of CF can have significant and sustained benefits for people with
the G551D mutation,” said Jeffrey Chodakewitz, M.D., Senior Vice
President and Chief Medical Officer at Vertex. “Our goal is to
develop combinations of medicines to treat many more people with CF
and to improve the benefit that these combinations of medicines may
provide. Data from the Phase 3 studies of lumacaftor in combination
with ivacaftor showed consistent evidence of clinical benefit in
lung function and other measures of the disease for people with two
copies of the F508del mutation and provided important support to
conduct further studies of combination regimens aimed at treating
people with one and two copies of the F508del mutation.”
Lumacaftor in Combination with
Ivacaftor
NDA and MAA Planned in the Fourth Quarter: In June 2014,
Vertex announced results from the Phase 3 TRAFFIC and TRANSPORT
studies of lumacaftor in combination with ivacaftor in people with
CF who have two copies of the F508del mutation. Based on the
results of these studies, Vertex plans to submit a New Drug
Application (NDA) in the United States and Marketing Authorization
Application (MAA) in Europe in the fourth quarter of 2014. The
global regulatory submissions will seek approval for the use of
lumacaftor (400 mg q12h) in combination with ivacaftor (250 mg
q12h) in people ages 12 and older with two copies of the F508del
mutation. The combination of lumacaftor and ivacaftor will be fully
co-formulated and dosed as two individual tablets every 12 hours
(four tablets daily). There are approximately 22,000 people ages 12
and older who have two copies of the F508del mutation in North
America, Europe and Australia, including approximately 8,500 in the
United States and approximately 12,000 in Europe.
Sustained Improvements in Lung Function Through 48 Weeks of
Treatment: Patients who completed 24 weeks of treatment in
either TRAFFIC or TRANSPORT were able to enter a Phase 3 rollover
study to receive a combination regimen. One thousand thirty-one
people started treatment in the rollover study, and at the time of
the interim analysis, approximately 25 percent of patients within
each arm of the rollover study had received an additional 24 weeks
of treatment for a total of 48 weeks of treatment (48 weeks of
treatment with a combination regimen for patients who received a
combination regimen in TRAFFIC and TRANSPORT; 24 weeks of treatment
with a combination regimen for patients who received placebo in
TRAFFIC and TRANSPORT).
The first interim data from this rollover study will be
presented at NACFC and showed that the initial improvements in lung
function (percent predicted forced expiratory volume in one second,
or ppFEV1) observed in the 24-week TRAFFIC and TRANSPORT studies
were sustained through 48 weeks of treatment with lumacaftor in
combination with ivacaftor. The pattern of response observed after
the initiation of combination dosing across all patients who
received placebo in TRAFFIC and TRANSPORT and subsequently received
a combination regimen in the rollover study was similar to that
seen in patients who received a combination regimen in TRAFFIC and
TRANSPORT.
At the time of the interim analysis, the safety and tolerability
results, including the rate of serious adverse events, were
consistent with those observed in the Phase 3 TRAFFIC and TRANSPORT
studies. Among patients new to treatment in the rollover study,
infective pulmonary exacerbation, cough, increased sputum,
haemoptysis, respiration abnormal and dyspnea were the most common
adverse events at the time of the interim analysis.
Results from TRAFFIC and TRANSPORT and from the interim analysis
of the rollover study will be presented as part of an oral invited
talk at NACFC ("Effect of lumacaftor in combination with ivacaftor
in patients with cystic fibrosis who are homozygous for
F508del-CFTR: Phase 3 TRAFFIC & TRANSPORT studies." Symposium
Session II on October 10 at 11:30 a.m. ET. Posters 249 and
250).
VX-661 in Combination with
Ivacaftor
VX-661 is Vertex’s second CFTR corrector and is being developed
to play a role in multiple combinations of CFTR modulators aimed at
treating people with CF who have one or two copies of the F508del
mutation.
Enrollment Complete in 12-week Phase 2 Study: VX-661 is
currently being evaluated in combination with ivacaftor as part of
a 12-week Phase 2b study in people ages 18 and older who have two
copies of the F508del mutation. Vertex today announced that this
study is fully enrolled and that data will be available in early
2015.
Pivotal Phase 3 Program of VX-661 Planned for First Half of
2015: Vertex today announced plans to initiate a pivotal Phase
3 clinical program of VX-661 in combination with ivacaftor in the
first half of 2015, pending regulatory discussions and data from
the ongoing 12-week Phase 2b study in people with two copies of the
F508del mutation. This Phase 3 program is expected to evaluate
efficacy and safety of VX-661 in combination with ivacaftor in
people with the following CFTR mutations:
- Two Copies of the F508del
Mutation, based on previously announced data from a Phase 2
study of VX-661 in combination with ivacaftor in people with two
copies of the F508del mutation to be presented at NACFC ("Phase 2
studies reveal additive effects of VX-661, an investigational CFTR
corrector, and ivacaftor, a CFTR potentiator, in patients with CF
who carry the F508del-CFTR mutation." An oral presentation of these
data will be delivered as part of an invited talk during Symposium
Session II on October 10 at 11:55 a.m. ET).
- One Copy of the F508del Mutation and
a Second Mutation That Results in a Gating Defect in the CFTR
Protein, based on data announced in mid-2014 from a Phase 2
proof-of-concept study in people with the F508del mutation and
G551D mutation to be presented at NACFC ("Addition of VX-661, an
investigational CFTR corrector, to ivacaftor, a CFTR potentiator,
in patients with CF and heterozygous for F508del/G551D-CFTR."
Poster 260).
- One Copy of the F508del Mutation and
a Second Mutation That Results in Residual CFTR Function, based
on data announced in mid-2014 from a Phase 2 proof-of-concept study
of ivacaftor in people with a residual function mutation to be
presented at NACFC (“Effect of ivacaftor in patients with cystic
fibrosis, residual CFTR function and FEV1 ≥ 40% of predicted,
N-of-1 study." Poster 196. An oral presentation of these data will
also be delivered during Workshop Session III on October 11 at 3:00
p.m. ET). Additionally, based on data from the Phase 2 study of
ivacaftor in people with a residual function mutation, referenced
above, Vertex plans to evaluate ivacaftor used as monotherapy in
people with these mutations as part of the pivotal program.
- One Copy of the F508del Mutation and
A Second Mutation That Results in Minimal CFTR Function – The
evaluation of people with one copy of the F508del mutation and one
copy of a CFTR mutation that results in minimal CFTR function as
part of the pivotal Phase 3 program would be the first evaluation
of VX-661 in combination with ivacaftor in people with these
mutations. To date, treatment with a combination of lumacaftor and
ivacaftor has not resulted in a significant improvement in lung
function for people with these mutations.
Planning for the pivotal Phase 3 program is underway to support
the initiation of enrollment in the first half of 2015, pending
regulatory discussions planned for later this year and the data
from the ongoing Phase 2b study, which are expected in early
2015.
Triple Combination of VX-661, Ivacaftor and a Next-Generation
Corrector: Vertex has multiple next-generation correctors in
the lead-optimization stage of research and expects to begin
clinical development of a next-generation corrector in 2015. In
vitro data showed that a triple combination of VX-661, ivacaftor
and a next-generation corrector resulted in increased chloride
transport in human bronchial epithelial cells with one or two
copies of the F508del mutation, as compared to the use of a single
corrector in combination with ivacaftor.
KALYDECO (ivacaftor)
Study of Ivacaftor in People with the R117H Mutation:
Data from a Phase 3 study of ivacaftor in people ages 6 and older
who have the R117H mutation will be presented at NACFC ("Effects of
ivacaftor in CF patients with R117H-CFTR." Poster 17. An oral
presentation of these data will also be delivered during Workshop
Session II on October 10 at 3:25 p.m. ET). As previously announced,
the Phase 3 study did not meet its primary endpoint of the absolute
change from baseline in percent predicted forced expiratory volume
in one second (ppFEV1) through 24 weeks of treatment, however a
pre-specified subset analysis in patients ages 18 and older showed
statistically significant improvements in lung function and other
key secondary endpoints. The safety and tolerability results
observed in this study were consistent with those observed in prior
Phase 3 studies of ivacaftor monotherapy in people with CF who have
the G551D or other gating mutations.
Based on the Phase 3 data, Vertex submitted an sNDA in the U.S.
and MAA variation in Europe for approval of ivacaftor in people
with the R117H mutation. Vertex’s sNDA for the use of ivacaftor in
people with the R117H mutation will be the subject of an FDA
Advisory Committee Meeting of the Pulmonary-Allergy Drugs Division
on October 21, 2014. In the United States, Vertex is seeking
approval of ivacaftor in people ages 6 and older with the R117H
mutation.
NDA and MAA Line Extension Submissions for Use of Ivacaftor
in Children Ages 2 to 5: Vertex today announced the submission
of an NDA in the United States for the approval of ivacaftor in
children with CF ages 2 to 5 who have one of the following nine
mutations in the CFTR gene: G551D, G178R, S549N, S549R, G551S,
G1244E, S1251N, S1255P or G1349D. Vertex expects to complete the
MAA line extension application in Europe this week. In the
United States and Europe, KALYDECO is currently approved for use in
people with CF ages 6 and older who have one of these nine
mutations.
The submissions were based on results announced today and being
presented at NACFC from an open-label Phase 3 study that was
designed to evaluate the pharmacokinetics and safety of
weight-based dosing of ivacaftor to support approval in children
ages 2 to 5 ("An open-label study of the safety, pharmacokinetics
& pharmacodynamics of ivacaftor in patients aged 2 to 5 years
with CF & a CFTR Gating Mutation: The KIWI Study." Poster 200.
An oral presentation of these data will also be delivered during
Workshop Session III on October 11 at 4:00 p.m. ET). The first part
of the study evaluated pharmacokinetics and safety of ivacaftor
treatment over four days to support the evaluation of ivacaftor for
24 weeks in the second part of the study. The primary endpoint of
the second part of the study was safety.
In the second part of the study (n=34), ivacaftor was generally
well tolerated and the majority of adverse events were mild or
moderate in severity. Five patients who had elevated liver enzymes
at baseline (greater than two times the upper limit of normal)
experienced further elevations of liver enzymes to greater than
eight times the upper limit of normal during the study. One patient
experienced a serious adverse event related to elevated liver
enzymes, and this patient discontinued treatment from the study.
For all five patients, liver enzymes returned to their baseline
levels following interruption of ivacaftor. Serious adverse events
occurred in 18 percent (6 of 34) of patients, and the most common
adverse events, regardless of dose group, were cough, vomiting,
nasal congestion, upper respiratory tract infection and
rhinorrhea.
In addition, secondary endpoints showed decreases in sweat
chloride and improvements in nutritional status as measured by
change in weight (weight-for-age z score) and body mass index
(BMI-for-age z score).
Based on results from this study, Vertex is seeking approval of
a 50 mg and 75 mg weight-based dose of ivacaftor for children ages
2 to 5. For children in this age group, a granule (mini-tablet)
formulation will be used to enable administration of ivacaftor in
soft foods as opposed to the current tablet formulation for people
6 years and older.
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 and the European Union, 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 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.
Investor Event Webcast
The company will host an investor event at 6:15 p.m. ET on
Friday, October 10 at NACF. To listen to management's live
presentation from the event, please dial (866) 501-1537 (U.S.) or
+1 (720) 545-0001 (International). The event will also be webcast
and a link to the live webcast can be accessed through Vertex's
website at www.vrtx.com in the "Investors" section under the
"Events and Presentations" link. Conference call and webcast
participants will be in a listen-only mode. An archived webcast of
the presentation will be available on the company's website.
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 of the press release, and the information provided
regarding (i) the planned Phase 3 pivotal program of VX-661 in
combination with ivacaftor; (ii) planned and ongoing studies of
ivacaftor, used alone or in combination with CFTR correctors; (iii)
the data that is expected to be presented at NACFC; (iv) plans to
submit regulatory applications, including plans to submit an NDA
and MAA for lumacaftor in combination with ivacaftor in the fourth
quarter of 2014; and (v) Vertex's next-generation corrector
research program. 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 data from the
company's development programs may not support registration or
further development of its compounds, that Vertex could experience
unforeseen delays in submitting regulatory filings, that regulatory
authorities may not approve, or approve on a timely basis,
lumacaftor in combination with ivacaftor or ivacaftor for
additional indications 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.
(VRTX-GEN)
Vertex Pharmaceuticals IncorporatedInvestors:Michael Partridge,
617-341-6108orKelly Lewis, 617-961-7530orMedia:North America: Zach
Barber, 617-341-6470orEurope and Australia: Megan
Goulart, +41 22 593 6066mediainfo@vrtx.com
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