-Mean absolute improvement in ppFEV1 of 13.8
percentage points from baseline at week 4 in people with one
F508del mutation and one minimal function mutation (F/MF) compared
to placebo (p<0.0001)-
-Mean absolute improvement in ppFEV1 of 10.0
percentage points from baseline at week 4 when VX-445 was added in
people with two F508del mutations (F/F) already receiving
tezacaftor and ivacaftor compared to control group of placebo added
to tezacaftor and ivacaftor (p<0.0001)-
-Safety and efficacy profile reported today
supports potential submission of a New Drug Application for the
VX-445 triple combination regimen-
-Vertex plans to seek global regulatory
approvals for either VX-659 or VX-445 triple combination regimen in
both F/F and F/MF patient populations concurrently based on final
24-week data for both regimens expected in the second quarter of
2019-
-U.S. NDA and EU MAA planned for the third and
fourth quarters of 2019, respectively-
In the prior version of this press release, VX-445 was
incorrectly referred to VX-659 in one instance. The release has
been updated accordingly.
The corrected release reads:
CORRECTING AND REPLACING TWO PHASE 3 STUDIES
OF THE TRIPLE COMBINATION OF VX-445, TEZACAFTOR AND IVACAFTOR MET
PRIMARY ENDPOINT OF IMPROVEMENT IN LUNG FUNCTION
(PPFEV1) IN PEOPLE WITH CYSTIC FIBROSIS
-Mean absolute improvement in ppFEV1 of 13.8
percentage points from baseline at week 4 in people with one
F508del mutation and one minimal function mutation (F/MF) compared
to placebo (p<0.0001)-
-Mean absolute improvement in ppFEV1 of 10.0
percentage points from baseline at week 4 when VX-445 was added in
people with two F508del mutations (F/F) already receiving
tezacaftor and ivacaftor compared to control group of placebo added
to tezacaftor and ivacaftor (p<0.0001)-
-Safety and efficacy profile reported today
supports potential submission of a New Drug Application for the
VX-445 triple combination regimen-
-Vertex plans to seek global regulatory
approvals for either VX-659 or VX-445 triple combination regimen in
both F/F and F/MF patient populations concurrently based on final
24-week data for both regimens expected in the second quarter of
2019-
-U.S. NDA and EU MAA planned for the third and
fourth quarters of 2019, respectively-
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced that treatment with the triple combination of the
next-generation corrector VX-445, 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 13.8 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-445 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-445 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-445 triple combination
regimen.
The Phase 3 data announced today for the VX-445 triple
combination regimen follow Phase 3 data announced in late 2018 for
the triple combination of VX-659, tezacaftor and ivacaftor that
also showed a safety and efficacy profile supportive of a potential
NDA submission. Given the similarity of the data for the 4-week
primary efficacy endpoint for the VX-659 and VX-445 regimens and
the near-term availability of the final 24-week data for both
regimens in the second quarter of 2019, Vertex plans to utilize
these final 24-week data to choose the best regimen to submit for
regulatory approvals globally. Because these submissions will
include the final 24-week data, Vertex will seek approval for
patients ages 12 and older with one F508del mutation and one
minimal function mutation and for patients with two F508del
mutations concurrently. Vertex plans to submit an NDA to the U.S.
FDA in the third quarter of 2019 and a Marketing Authorization
Application (MAA) in Europe in the fourth quarter of 2019 for
either the VX-659 or VX-445 triple combination regimen. The company
also plans to disclose more detailed data from the Phase 3 studies
of the selected triple combination regimen, including 24-week data
from the study in patients with one F508del mutation and one
minimal function mutation, in the second quarter of 2019.
“Both the VX-659 and VX-445 triple combination regimens showed
highly consistent and significant improvements in lung function
across our Phase 3 programs, underscoring the important clinical
benefit that a triple combination regimen may provide to patients
with two F508del mutations and to those with one F508del and one
minimal function mutation,” said Reshma Kewalramani, M.D.,
Executive Vice President, Global Medicines Development and Medical
Affairs and Chief Medical Officer at Vertex. “We look forward to
submitting global regulatory applications for one of these triple
combination regimens for both patient populations later this
year.”
About the VX-445 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-445, tezacaftor and
ivacaftor compared to triple placebo for 24 weeks. The study
randomized 405 patients, and 403 patients received at least one
dose of either the VX-445 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. 402 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-445 triple
combination regimen for patients with one F508del mutation and one
minimal function mutation.
Topline Data:
Treatment with the triple combination of VX-445, tezacaftor and
ivacaftor resulted in a mean absolute improvement in ppFEV1 of 13.8
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-445 triple combination regimen was 13.6 percentage
points from baseline at week 4. The mean absolute within-group
change in ppFEV1 for those who received triple placebo was -0.2
percentage points from baseline at week 4.
The VX-445 triple combination regimen was generally well
tolerated in this study. The safety profile reflects all available
safety data for all patients at the time of the interim analysis,
including 246 patients who had reached the week 12 visit (123
patients who were randomized to the VX-445 triple combination
regimen and 123 patients randomized to triple placebo) and 65
patients who had completed the 24-week treatment period (29
patients randomized to receive the VX-445 triple combination
regimen and 36 patients randomized to receive triple placebo).
This study is ongoing to evaluate the VX-445 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.
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-445
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-445 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-445, tezacaftor, and ivacaftor compared to placebo, tezacaftor
and ivacaftor. The study randomized 108 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 107 of the 108 patients who were
randomized received at least 1 dose of either the triple
combination of VX-445, 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-445, 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=107) patients completed the study. The safety
and efficacy profile in this study supports the potential
submission of an NDA for the VX-445 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-445 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-445
in triple combination with tezacaftor and ivacaftor was 10.4
percentage points at week 4. The mean absolute within-group change
in ppFEV1 from baseline for those who received placebo, tezacaftor
and ivacaftor was 0.4 percentage points at week 4.
The VX-445 triple combination regimen was generally well
tolerated in this study. All of the 107 patients who received
either the triple combination of VX-445, tezacaftor and ivacaftor
or placebo, tezacaftor and ivacaftor completed the 4-week triple
combination treatment period.
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-445
triple combination regimen. All 107 of the patients who completed
the study elected to enter the open-label extension study.
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
third paragraph, and the information provided regarding (i) the
plan to seek global regulatory approvals for a triple combination
regimen in both F/MF and F/F populations, (ii) the expected timing
of the NDA and MAA submissions for a triple combination therapy and
(iii) the plan to provide additional data regarding the selected
regimen in the second quarter of 2019. 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 triple combination studies are 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, 617-341-6108orEric Rojas,
617-961-7205orZach Barber, 617-341-6470
Media:617-341-6992mediainfo@vrtx.com
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