-Enrollment complete for TRAFFIC and TRANSPORT Phase 3 studies of
lumacaftor (VX-809) in combination with ivacaftor for people with two
copies of the F508del mutation (homozygous); data expected in mid-2014-
-12-week Phase 2 study of VX-661 in combination with ivacaftor
planned for people with two copies of the F508del mutation; Phase 2
study of VX-661 in combination with KALYDECO now enrolling to explore
the potential to enhance clinical benefit in people with CF who have the
-Data from label-expansion study in people with non-G551D gating
mutations and from PERSIST open-label rollover study to be presented at
North American Cystic Fibrosis Conference this week-
SALT LAKE CITY--(BUSINESS WIRE)--
Pharmaceuticals Incorporated (Nasdaq: VRTX) today provided a
comprehensive update on recent progress in its research and development
activities in cystic fibrosis (CF) aimed at helping more people with CF
and enhancing the clinical benefit for these patients with our approved
and investigational medicines. Vertex today announced that the TRAFFIC
and TRANSPORT Phase 3 studies of lumacaftor (VX-809) in combination with
ivacaftor in people with two copies of the F508del mutation are fully
enrolled. Data from these studies are expected in mid-2014, and Vertex
plans to submit a New Drug Application (NDA) in the U.S. and a Marketing
Authorization Application (MAA) in Europe in the second half of 2014 for
the combination of lumacaftor and ivacaftor. Vertex also today provided
updates on multiple ongoing label-expansion studies for ivacaftor,
ongoing and planned Phase 2 combination studies of lumacaftor and
ivacaftor and VX-661 and ivacaftor, and research efforts aimed at
beginning clinical development of a next-generation corrector.
These updates were made in conjunction with the 27th Annual North
American Cystic Fibrosis Conference (NACFC) in Salt Lake City where
additional data from a study of ivacaftor in people with non-G551D
gating mutations and data from the PERSIST open-label rollover study
will be presented. The company will webcast remarks from its investor
presentation at the conference at 2:45 p.m. ET on Friday, October 18.
The webcast can be accessed at www.vrtx.com/nacfc2013.
"KALYDECO was the first medicine to treat the underlying cause of CF,
and we believe that KALYDECO is just the first step of our work in CF,"
said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief
Medical Officer at Vertex. "Our goal in CF is to help many more people
with this disease and to evaluate multiple combinations of CFTR
modulators aimed at providing further benefit for people with CF."
KALYDECOTM (ivacaftor) is currently approved for people with
CF ages 6 and older who have at least one copy of the G551D mutation in
the cystic fibrosis transmembrane conductance regulator (CFTR)
gene. More than 2,000 people with CF ages 6 and older have at least one
copy of the G551D mutation in North America, Europe and Australia.
Vertex has multiple studies planned and underway to evaluate whether
ivacaftor may help additional people with CF who have other mutations
that may respond to ivacaftor treatment. More than 7,000 people with CF,
including those with the G551D mutation, have CFTR mutations that may
respond to ivacaftor treatment. The company is also conducting studies
to evaluate a combination of ivacaftor and a corrector in people with
two copies of the most common CFTR mutation, F508del. Vertex today
provided the following updates:
Global Availability of KALYDECO: KALYDECO is currently
available to eligible patients in England, Scotland, Northern Ireland,
Wales, the Republic of Ireland, France, Germany, the Netherlands,
Austria, Denmark, Sweden, Norway, Greece and the U.S. Vertex is in
active discussions with relevant agencies in Australia and Canada
regarding public reimbursement of KALYDECO in these countries.
PERSIST Data Presented at NACFC and Submitted to U.S. FDA: Data
from the open-label PERSIST study will be presented as a poster at
NACFC. PERSIST is an ongoing rollover study of people with CF ages 6
and older with a G551D mutation who took part in the Phase 3 STRIVE
and ENVISON studies of KALYDECO. The data from PERSIST showed that 144
weeks of continuous treatment with KALYDECO provided durable treatment
effects in lung function (as measured by FEV1), weight and
other measures. The safety profile was consistent with what was
observed in the 48-week Phase 3 studies that supported the approval of
KALYDECO. The PERSIST data have been submitted to the U.S. Food and
Drug Administration (FDA) for review for potential inclusion in the
Studies to Expand Number of People Eligible for Ivacaftor
Multiple ongoing studies of ivacaftor monotherapy are designed to
evaluate whether additional people with CF may benefit from treatment
with ivacaftor alone. These studies include three Phase 3
label-expansion studies and a Phase 2 proof-of-concept study:
Gating Mutations Study: In September, Vertex announced
submission of a supplemental NDA (sNDA) for people with CF ages 6 and
older who have at least one non-G551D gating mutation. Vertex also
recently submitted an MAA variation in Europe for the same group of
people with CF. The sNDA and MAA variation submissions were based on
data from a Phase 3 study that showed statistically significant
improvements in lung function (FEV1), and other measures of
disease. 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 mutation.
Additional data from this study will be presented at NACFC as part of
Symposium III, "CFTR: Matching CFTR Mutations and Drugs," on October
19, 10:30 a.m. - 12:20 p.m. MT. In North America, Europe and
Australia, approximately 400 people age 6 and older have at least one
non-G551D gating mutation.
R117H Study: A Phase 3 study of people ages 6 and older with
one copy of the R117H mutation is ongoing and fully enrolled. Vertex
expects data to be available from this study at the end of 2013 to
support a potential sNDA submission in early 2014. A potential MAA
variation is planned for the second quarter of 2014. In North America,
Europe and Australia, approximately 1,100 people ages 6 and older have
at least one R117H mutation. People who have the R117H mutation
exhibit a range of severity and signs and symptoms of the disease.
Study in Children Ages 2 to 5 with Gating Mutations: A Phase 3
study of ivacaftor in children with CF ages 2 to 5 who have a gating
mutation is ongoing and fully enrolled. Data from this study are
expected in the second quarter of 2014 to support a potential sNDA
submission in the second half of 2014. In North America, Europe and
Australia, approximately 300 children ages 2 to 5 have a gating
Residual Function Study: Enrollment is complete in a Phase 2
proof-of-concept study evaluating ivacaftor in people with CF who have
clinical evidence of residual CFTR function. Data from this study are
expected in the second quarter of 2014. In North America, Europe and
Australia, more than 3,000 people ages 6 and older have non-R117H CFTR
mutations that result in residual function.
Phase 3 Program in People with Two Copies
(homozygous) of the F508del Mutation
Phase 3 TRAFFIC and TRANSPORT Studies: Vertex recently
completed enrollment of the Phase 3 TRAFFIC and TRANSPORT studies
evaluating lumacaftor (VX-809) in combination with ivacaftor in people
with CF ages 12 and older who have two copies (homozygous) of the
F508del mutation. Vertex expects data from these studies to be
available in mid-2014 to support the potential submission of an NDA
and MAA for the combination in people homozygous for the F508del
mutation in the second half of 2014.
Vertex also recently began enrollment in two additional studies of
lumacaftor in combination with ivacaftor as part of the Phase 3
program. These additional studies are:
Study in Children Ages 6 to 11: Vertex recently completed
dosing in the pharmacokinetics portion of a Phase 2 study of
VX-809 in combination with ivacaftor in children with CF ages 6 to
11 who have two copies of the F508del mutation. Enrollment in the
second part of this study is expected to begin in the first
quarter of 2014. Data from this study is expected be used for
potential subsequent registration of the combination in children
ages 6 to 11 in the U.S.
Study in People Ages 18 and Older with One Copy (heterozygous)
of the F508del mutation: Vertex recently began enrollment in
an 8-week exploratory Phase 2 study of lumacaftor in combination
with ivacaftor in people 18 and older with one copy (heterozygous)
of the F508del mutation on one allele and a second mutation
that is not expected to respond to either ivacaftor or lumacaftor
alone. This study will evaluate the twice daily (q12h)
administration of VX-809 (400mg) and ivacaftor (250mg) to provide
additional safety and lung function data on the combination in
More than 28,000 people ages 6 and older have two copies of the F508del
mutation in North America, Europe and Australia, and more than 17,000
people ages 6 and older have one copy of the F508del mutation and a
mutation not expected to respond to ivacaftor treatment.
VX-661 in Combination with Ivacaftor
12-Week Phase 2b Study of VX-661 and Ivacaftor in People with Two
Copies of the F508del Mutation: Following recent discussions with
regulatory authorities, Vertex is preparing to conduct a 12-week study
of VX-661 in combination with ivacaftor in people with CF who have two
copies of the F508del mutation. The study is designed to evaluate
safety, efficacy and dose-response information to characterize VX-661
for further clinical development. Enrollment in this study is expected
to begin in the first quarter of 2014, pending protocol approval from
4-Week Study of VX-661 in Combination with KALYDECO in People with
One Copy of Both the G551D and F508del mutation: Vertex recently
began enrollment in a Phase 2 study evaluating a 4-week regimen of
VX-661 in combination with KALYDECO in people with one copy of the
G551D mutation and one copy of the F508del mutation. This is the first
proof-of-concept study of a combination of a corrector and KALYDECO in
people with these mutations. This study is intended to explore whether
the addition of a corrector to treatment with KALYDECO can further
enhance the clinical benefit received from KALYDECO alone in people
with the G551D and F508del mutations. This combination treatment
regimen is supported by in vitro data showing enhanced CFTR
function with the combination of VX-661 and ivacaftor. Data from this
study are expected in the first quarter of 2014.
Prioritization of VX-661: Based on the emerging profiles for
VX-661 and VX-983, Vertex has prioritized VX-661 over VX-983. The
company does not intend to further develop VX-983.
Vertex's goal is to advance a next-generation corrector into clinical
development by the end of 2014. Next-generation correctors could be
evaluated as part of potential dual-corrector regimens. The proposed
use of a dual-corrector combination regimen is supported by in
vitro data that showed a combination of two correctors with
ivacaftor 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.
Additional NACFC Presentations
At NACFC, Fred Van Goor, Ph.D., Head of Biology for Vertex's CF program,
and David Rodman, M.D., Vice President of Clinical Development for
Vertex's CF program, will participate in invited talks regarding their
work to discover and develop medicines that target the underlying cause
of CF. The talks will take place during Symposium Sessions II and III:
"Matching Novel Therapies to CF-Causing Mutations in Cell-based
Systems." Fred Van Goor, Ph.D, will deliver an invited talk during
Symposium Session III, "CFTR: Matching CFTR Mutations & Drugs," on
October 19 at 11:30 a.m. MT.
"Lessons Learned From the Development of First Generation CFTR
Modulators." David Rodman, M.D., will deliver an invited talk during
Symposium II, "NT/CFTR: Advances in the Therapeutic Pipeline for CFTR
Repair (Combination)," on October 18 at 11:55 a.m. MT.
KALYDECO™ (ivacaftor) is the first medicine to treat the underlying
cause of CF in people with the G551D mutation 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, by the European Medicines Agency in July
2012, by Health Canada in November 2012 and by the Therapeutic Goods
Administration in Australia in July 2013 for use in people with CF ages
6 and older who have at least one copy of the G551D mutation in the CFTR
gene. A New Medicine Application (NMA) for KALYDECO has been submitted
to Medsafe, the New Zealand Medicines and Medical Devices Safety
Authority, and has been granted priority assessment.
Vertex retains worldwide rights to develop and commercialize KALYDECO.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO™ (ivacaftor)
Ivacaftor (150mg 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.
Ivacaftor is not for use in people with CF due to other mutations in the CFTR gene.
It is not effective in patients with CF with 2 copies of the F508del
mutation (F508del/F508del) in the CFTR gene. The
efficacy and safety of ivacaftor in children younger than 6 years of age
have not been evaluated.
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 which may
diminish effectiveness. Therefore, co-administration is not recommended.
The dose of ivacaftor must be adjusted when used concomitantly with
potent and moderate CYP3A inhibitors. The dose of ivacaftor must be
adjusted 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
Please see full U.S. Prescribing Information for KALYDECO at www.KALYDECO.com,
the EU Summary of Product Characteristics for KALYDECO at http://goo.gl/N3Tz4,
the Canadian Product Monograph for KALYDECO at www.vrtx.ca
and the Australian Consumer Medical Information and Product Information
for KALYDECO at http://bit.ly/18wlMld.
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
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
1,800 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
absence of working CFTR protein 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,
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.
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 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 2,000 employees around the world, and for
three years in a row, Science magazine has named Vertex one of its 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, including, without
limitation, Dr. Kauffman's statements in the third paragraph of this
press release and statements regarding (i) Vertex's ongoing and planned
studies evaluating ivacaftor monotherapy, lumacaftor (VX-809) in
combination with ivacaftor, and VX-661 in combination with ivacaftor,
including its expectations regarding the timing of enrollment and the
receipt of data from these studies and potential timelines for NDA, sNDA
and other regulatory submissions, and (ii) Vertex's ongoing research
program for the discovery and development of next generation CFTR
corrector compounds, including its goal of advancing a next-generation
corrector into clinical development by the end of 2014. While Vertex
believes the forward-looking statements contained in this press release
are accurate, those statements are subject to risks and uncertainties
that could cause actual outcomes to vary materially from the outcomes
referenced in the forward-looking statements. These risks and
uncertainties include, among other things: the sNDA and MAA variation
for ivacaftor for people ages 6 and older who have at least one
non-G551D mutation may not be approved; studies of ivacaftor, ivacaftor
in combination with lumacaftor, and ivacaftor in combination with VX-661
may be delayed or prevented; that the outcomes of Vertex's ongoing and
planned clinical studies may not support registration or further
development of its compounds due to safety, efficacy or other reasons;
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 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.
Vertex Pharmaceuticals Incorporated
Kelly Lewis, 617-961-7530
Source: Vertex Pharmaceuticals Incorporated
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