-Mean absolute improvement in ppFEV1 of 14.0
percentage points from baseline at week 4 in people with one
F508del mutation and one minimal function mutation compared to
placebo (p<0.0001)-
-Mean absolute improvement in ppFEV1 of 10.0
percentage points from baseline at week 4 when VX-659 was added in
people with two F508del mutations already receiving tezacaftor and
ivacaftor compared to control group of placebo added to tezacaftor
and ivacaftor (p<0.0001)-
-Safety and efficacy profile supports potential
submission of a New Drug Application for the VX-659 triple
combination regimen-
-Two Phase 3 studies of the triple combination
of VX-445, tezacaftor and ivacaftor are now fully enrolled with
data expected in the first quarter of 2019-
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced that treatment with the triple combination of the
next-generation corrector VX-659, tezacaftor and ivacaftor resulted
in statistically significant improvements in lung function (percent
predicted forced expiratory volume in one second, or ppFEV1) in two
Phase 3 studies in people with cystic fibrosis (CF). Data from a
pre-specified interim analysis of the Phase 3 study in people with
one F508del mutation and one minimal function mutation showed a
mean absolute improvement in ppFEV1 of 14.0 percentage points from
baseline at week 4 of treatment compared to placebo (p<0.0001).
In the Phase 3 study in people with two F508del mutations, the
addition of VX-659 in patients already receiving tezacaftor and
ivacaftor resulted in a mean absolute improvement in ppFEV1 of 10.0
percentage points from baseline at week 4 of treatment compared to
the control group in whom placebo was added to tezacaftor and
ivacaftor (p<0.0001). The VX-659 triple combination regimen was
generally well tolerated, and the safety and efficacy profile from
the results released today supports the potential submission of a
New Drug Application (NDA) for the VX-659 triple combination
regimen.
Vertex also today announced that enrollment is complete for the
two Phase 3 studies of the triple combination of the
next-generation corrector VX-445, tezacaftor and ivacaftor in
people with CF with one F508del mutation and one minimal function
mutation and in people with two F508del mutations. Vertex remains
on track to report topline data from both Phase 3 studies of the
VX-445 triple combination regimen in the first quarter of 2019.
The data expected in the first quarter of 2019 for VX-445 and
the data reported today for VX-659 will enable Vertex to choose the
best regimen to submit for potential regulatory approvals globally
and will provide the basis for potential submission of an NDA for a
triple combination regimen to the U.S. FDA no later than
mid-2019.
“These data mark a major milestone in our efforts to develop new
CF medicines as they underscore the important clinical benefit that
a triple combination regimen may provide to the vast majority of CF
patients who have at least one F508del mutation,” said Reshma
Kewalramani, M.D., Executive Vice President, Global Medicines
Development and Medical Affairs and Chief Medical Officer at
Vertex. “We plan to evaluate data for the VX-445 and VX-659 triple
combination regimens in the first quarter of next year and to
choose the best regimen to submit for potential approval with the
goal of bringing forward a new treatment option to those with one
F508del mutation and one minimal function mutation and to those
with two F508del mutations as rapidly as possible.”
About the VX-659 Phase 3 Study in People with One F508del
Mutation and One Minimal Function Mutation
The data announced today for people ages 12 and older with one
F508del mutation and one minimal function mutation are from an
ongoing, randomized, double-blind, placebo-controlled Phase 3 study
evaluating the triple combination of VX-659, tezacaftor and
ivacaftor compared to triple placebo for 24 weeks. The study
randomized 385 patients, and 382 patients received at least one
dose of either the VX-659 triple combination regimen or triple
placebo. In the U.S., the primary endpoint of the study is the mean
absolute change in ppFEV1 from baseline at week 4 of triple
combination treatment compared to triple placebo. The data
announced today are from a pre-specified interim analysis that
evaluated the primary endpoint at week 4. 380 patients had
completed the week 4 visit of the study at the time of the interim
analysis. The safety and efficacy profile in the interim analysis
supports the potential submission of an NDA for the VX-659 triple
combination regimen for patients with one F508del mutation and one
minimal function mutation.
Topline Data:
Treatment with the triple combination of VX-659, tezacaftor and
ivacaftor resulted in a mean absolute improvement in ppFEV1 of 14.0
percentage points from baseline at week 4 compared to triple
placebo (p<0.0001), which was the primary endpoint of the study.
The mean absolute within-group improvement in ppFEV1 for those who
received the VX-659 triple combination regimen was 13.0 percentage
points from baseline at week 4. The mean absolute within-group
change in ppFEV1 for those who received triple placebo was -1.0
percentage points from baseline at week 4.
The VX-659 triple combination regimen was generally well
tolerated in this study, and the safety profile reflects all
available safety data for all patients at the time of the interim
analysis, including 302 patients who had reached the week 12 visit
(151 patients who were randomized to receive the VX-659 triple
combination regimen and 151 patients randomized to receive triple
placebo) and 58 patients who had completed the 24-week treatment
period (28 patients randomized to receive the VX-659 triple
combination regimen and 30 patients randomized to receive triple
placebo).
This study is ongoing to evaluate the VX-659 triple combination
regimen for a total of 24 weeks and will generate additional safety
and efficacy data and data for key secondary endpoints, including
the number of pulmonary exacerbations, change in sweat chloride,
change in patient-reported outcomes as measured by the respiratory
domain score of the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
and change in body mass index, among others. To preserve the
integrity of this ongoing study and the ongoing Phase 3 studies of
VX-445, Vertex intends to wait to disclose additional safety and
efficacy data for this study, including key secondary endpoints,
until the second half of 2019 following the completion of the
VX-659 and VX-445 Phase 3 studies.
Open-Label Extension Study:
All patients who complete treatment in the 24-week study,
regardless of treatment assignment, are given the opportunity to
enroll in a rollover study where all patients receive the VX-659
triple combination regimen. All patients who had completed the
study at the time of the interim analysis elected to enter the
open-label extension study.
About the VX-659 Phase 3 Study in People with Two F508del
Mutations
The data announced today for people with two F508del mutations
are from a randomized, double-blind, controlled Phase 3 study that
evaluated four weeks of treatment with the triple combination of
VX-659, tezacaftor, and ivacaftor compared to placebo, tezacaftor
and ivacaftor. The study randomized 111 patients ages 12 years or
older who have two F508del mutations. All patients received
tezacaftor in combination with ivacaftor during a 4-week run-in
prior to randomization, and all of the 111 patients who were
randomized received at least 1 dose of either the triple
combination of VX-659, tezacaftor and ivacaftor or placebo,
tezacaftor and ivacaftor. The primary endpoint of the study was the
mean absolute change in ppFEV1 from baseline (end of the 4-week
tezacaftor/ivacaftor run-in) at week 4 of triple combination of
VX-659, tezacaftor and ivacaftor compared to placebo in combination
with tezacaftor and ivacaftor. The data announced today reflect
topline data from the primary efficacy and safety analysis
conducted once all (n=111) patients completed the study. The safety
and efficacy profile in this study supports the potential
submission of an NDA for the VX-659 triple combination regimen for
patients with two F508del mutations.
Topline Data:
Data from this study showed a mean absolute improvement in
ppFEV1 of 10.0 percentage points from baseline at week 4 when
VX-659 was added in patients who were already receiving tezacaftor
in combination with ivacaftor compared to those in whom placebo was
added to tezacaftor and ivacaftor (p<0.0001), which was the
primary endpoint of the study. The mean absolute within-group
improvement in ppFEV1 from baseline for those who received VX-659
in triple combination with tezacaftor and ivacaftor was 10.2
percentage points at week 4. The mean absolute within-group change
in ppFEV1 from baseline for those who received placebo, tezacaftor
and ivacaftor was 0.3 percentage points at week 4.
The VX-659 triple combination regimen was generally well
tolerated in this study. All of the 111 patients who were
randomized in the study completed the 4-week triple combination
treatment period.
To preserve the integrity of the ongoing Phase 3 studies of
VX-659 and VX-445, Vertex intends to wait to disclose additional
safety and efficacy data for this study, including key secondary
endpoints, until the second half of 2019 following the completion
of the VX-659 and VX-445 Phase 3 studies.
Open-Label Extension Study: Similar to the study in
people with one F508del mutation and one minimal function mutation,
all patients who completed treatment, regardless of treatment
assignment, were given the opportunity to enroll in a rollover
study where all patients received the VX-659 triple combination
regimen. 110 of the 111 patients who completed the study elected to
enter the open-label extension study.
Enrollment Complete for the VX-445 Phase 3 Studies
Vertex today announced that it has completed enrollment for the
two Phase 3 studies evaluating the triple combination of VX-445,
tezacaftor and ivacaftor in people with one F508del mutation and
one minimal function mutation and in people with two F508del
mutations. The study designs are the same as were used for the
VX-659 Phase 3 program noted above.
Similar to the VX-659 program, the Phase 3 study of the VX-445
triple combination regimen in patients with one F508del mutation
and one minimal function mutation was designed with a pre-specified
interim analysis to evaluate the U.S. primary endpoint of ppFEV1 at
week 4. Data from the VX-445 interim analysis are expected in the
first quarter of 2019. Similar to VX-659, Vertex expects to
disclose in the first quarter of 2019 only the topline results for
the primary 4-week efficacy endpoints of the VX-445 Phase 3 studies
and whether the safety and efficacy profile observed supports a
potential NDA submission. Vertex intends to disclose additional
safety and efficacy data, including key secondary endpoints, for
the VX-445 studies in the second half of 2019 following the
completion of the VX-659 and VX-445 Phase 3 studies.
Submissions for Approval Outside the U.S.
Data from these studies of VX-659 and VX-445 will also be used
for regulatory submissions outside of the U.S. planned for late
2019.
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 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
cells 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.
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, Australia and Latin America. 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 nine 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), SYMDEKO®
(tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 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. Kewalramani’s statements in the
fourth paragraph, and the information provided regarding (i) the
company’s plans regarding announcement of additional data from its
ongoing studies, including topline data from the ongoing VX-445
triple combination study and (ii) the company’s plans regarding the
potential submission of regulatory filings for its triple
combination regimens in the U.S. and outside of the U.S. 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 the topline data reported in this press
release is based on a pre-specified interim analysis of the ongoing
VX-659 triple combination studies and that final data may differ,
that the VX-445 triple combination study is ongoing, that the
company could experience unforeseen delays in submitting regulatory
filings, that regulatory authorities may not approve, or approve on
a timely basis, a triple-combination regimen 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)
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Investors:Michael Partridge, 617-341-6108 orEric Rojas,
617-961-7205 orZach Barber,
617-341-6470Media:617-341-6992mediainfo@vrtx.com
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