-Global Phase 3 study to enroll approximately
100 patients with the most common genetic form of the disease-
-Phase 2 data showed mean absolute improvement
in ppFEV1 of 9.7 percentage points when VX-659 was added in
people with CF who have two F508del mutations who were already
receiving tezacaftor and ivacaftor; triple combination regimen was
generally well tolerated-
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced that it is initiating a Phase 3 study of VX-659,
tezacaftor and ivacaftor as an investigational triple combination
regimen for people with cystic fibrosis (CF) who have two copies of
the F508del mutation, the most common genetic form of the disease.
The study will enroll approximately 100 patients, and the primary
endpoint of the study is the mean absolute change from baseline in
percent predicted forced expiratory volume in one second (ppFEV1)
at week four of treatment. The study is designed to support the
submission of an application for approval in patients with two
copies of the F508del mutation in the U.S. using data from the
4-week primary efficacy endpoint together with 24-week safety data
generated from the recently initiated Phase 3 study in patients
with one F508del mutation and one minimal function mutation.
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The initiation of the Phase 3 study in people with CF who have
two copies of the F508del mutation is based on data announced today
from a Phase 2 study that showed a mean absolute improvement in
ppFEV1 of 9.7 percentage points from baseline through week four of
treatment when VX-659 (400 mg) was added in people with CF who have
two F508del mutations and were already receiving tezacaftor in
combination with ivacaftor. In the Phase 2 study, the VX-659 triple
combination regimen was generally well tolerated, the majority of
adverse events were mild to moderate in severity and there were no
discontinuations due to adverse events.
“We continue to make rapid and significant progress in our
efforts to advance our two triple combination regimens into Phase 3
development, with an ultimate goal of bringing the best triple
combination to patients as quickly as possible,” said Jeffrey
Chodakewitz, M.D., Executive Vice President and Chief Medical
Officer at Vertex. “The first Phase 3 study we announced in
February is designed to support approval of the VX-659 triple
combination in patients with one F508del mutation and one minimal
function mutation who currently have no treatment that addresses
the underlying cause of disease. This second study is designed to
enable us to broaden the potential label for this regimen to
include those with the most common genetic form of cystic
fibrosis.”
About the Phase 3 Study
The randomized, double-blind, controlled Phase 3 study will
evaluate four weeks of treatment with VX-659 or placebo in
combination with tezacaftor and ivacaftor in approximately 100
patients ages 12 years or older who have two F508del mutations.
Approximately 50 patients will receive VX-659, tezacaftor and
ivacaftor and approximately 50 will receive placebo, tezacaftor and
ivacaftor. All patients will receive tezacaftor in combination with
ivacaftor during a 4-week run-in prior to the start of the triple
combination treatment period. The primary endpoint of the study is
the mean absolute change in lung function (ppFEV1) from baseline
(end of the 4-week tezacaftor/ivacaftor run-in) at week four of
treatment with VX-659 in combination with tezacaftor and ivacaftor
compared to those who received placebo, tezacaftor and ivacaftor.
Key secondary endpoints will also be measured at week four and
include changes in patient-reported outcomes as measured by the
respiratory domain of the Cystic Fibrosis Questionnaire-Revised
(CFQ-R) and change in sweat chloride.
The study will evaluate a fixed-dose combination of VX-659 (240
mg) with tezacaftor (100 mg) and ivacaftor (150 mg) in the morning
followed by ivacaftor (150 mg) in the evening, which is the same
dosing regimen being evaluated in the ongoing Phase 3 study in
patients with one F508del mutation and one minimal function
mutation. An open-label extension study will be conducted where all
eligible patients, including those who received placebo, tezacaftor
and ivacaftor, will receive the triple combination regimen for up
to an additional 96 weeks.
The study is designed to support an application for U.S. Food
and Drug Administration (FDA) approval of the VX-659 triple
combination regimen in patients with two copies of the F508del
mutation based on data from the 4-week primary efficacy analysis
and secondary safety analysis and on 24-week safety data from the
Phase 3 study in patients with one F508del mutation and one minimal
function mutation. Vertex plans to use the study in patients with
two F508del mutations to broaden the potential label for the VX-659
triple combination regimen and does not anticipate that the study
will impact its initial planned submission of a New Drug
Application to the U.S. FDA for patients with one F508del mutation
and one minimal function mutation. Data from the study in patients
with two F508del mutations will also be used to support planned
regulatory submissions in Europe and other regions.
Vertex plans to initiate multiple additional Phase 3 studies of
VX-659 and VX-445 triple combination regimens in 2018. Regulatory
discussions are ongoing regarding the design of these additional
Phase 3 studies.
Phase 2 Data in Patients with Two F508del Mutations
The data announced today are from Part 2 of an ongoing
randomized, double-blind, controlled Phase 2 study where the
primary objectives are safety, tolerability and efficacy as
assessed by mean absolute change in ppFEV1 from baseline (end of
the 4-week tezacaftor/ivacaftor run-in period) through week four of
treatment. Secondary endpoints include absolute change in sweat
chloride and change in the CFQ-R respiratory domain score, among
others.
All patients received a 4-week run-in of tezacaftor in
combination with ivacaftor. Patients were then randomized to add
either VX-659 or placebo to tezacaftor and ivacaftor for four
weeks. After the 4-week triple combination dosing period, all
patients received four weeks of tezacaftor and ivacaftor, followed
by a 4-week safety follow-up period. In the triple combination
dosing period of the study, patients received a morning dose of
VX-659 (400 mg), or placebo, in addition to a fixed-dose
combination of tezacaftor (100 mg) and ivacaftor (150 mg) in the
morning followed by an evening dose of ivacaftor (150 mg)
alone.
Safety Data: The triple combination regimen was generally
well tolerated. The majority of adverse events were mild or
moderate. No serious adverse events were reported in the triple
combination group and one serious adverse event (pulmonary
exacerbation) was reported in the group that received tezacaftor in
combination with ivacaftor. There were no discontinuations due to
adverse events in either treatment group, and there were no
treatment interruptions. The most common adverse events (>10%),
regardless of treatment group, were cough, infective pulmonary
exacerbation, nasal congestion, nausea, sputum increased, vomiting,
headache, abdominal pain upper, blood creatine phosphokinase
increased, diarrhea, oropharyngeal pain, rash and upper respiratory
tract infection.
Efficacy Data: This part of the study evaluated the
addition of VX-659, or placebo, to ongoing tezacaftor/ivacaftor
treatment for a 4-week triple combination dosing period in 29
patients who have two F508del mutations (11 in the
placebo/tezacaftor/ivacaftor arm, 18 in VX-659 triple combination
arm). A summary of the within-group lung function and sweat
chloride data is provided below:
VX-659 Added to Ongoing Treatment with
Tezacaftor and Ivacaftor in Patients withTwo F508del
Mutations
Mean Absolute Within-Group
ChangeFrom Baseline Through Day 29*
Mean Absolute Within-Group
Change in ppFEV1(percentage points)
Mean Absolute Within-Group
Change in SweatChloride (mmol/L)
Placebo + tezacaftor (100mg QD) +ivacaftor
(150mg q12h)
0.0(p=0.9926)
+3.0(p=0.2977)
VX-659 (400mg QD) + tezacaftor(100mg QD) +
ivacaftor (150mg q12h)
+9.7(p<0.0001)
-42.2(p<0.0001)
* all p-values are within group p-values
based on mixed effect models; values expressed as ‘ThroughDay 29'
are the average of Day 15 and Day 29 measures
A secondary endpoint in the study measured mean absolute
within-group change in the respiratory domain of CFQ-R,1 a
validated patient-reported outcome measure, at Day 29. The mean
absolute improvement for patients who received the VX-659 triple
combination was 19.5 points. The improvement for those who received
placebo in addition to tezacaftor and ivacaftor was 2.9 points.
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 cystic fibrosis
transmembrane conductance regulator (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
cell 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 and Australia. 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 eight 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-440, VX-152, 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. Chodakewitz's statements in the
third paragraph and the information provided regarding (i) the
timing and design of Vertex's Phase 3 study for VX-659, (ii) the
potential to use the study to support regulatory applications,
(iii) the relationship between the study in patients with two
copies of the F508del mutation and the study that the company is
conducting in patients with one F508del mutation and one minimal
function mutation and (iv) Vertex’s plans to initiate multiple
additional Phase 3 studies of VX-659 and VX-445 triple combination
regimens in 2018. 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: (i) that Vertex could
experience unforeseen delays in initiating its Phase 3 studies to
evaluate VX-659 and/or VX-445, (ii) that data from the Phase 3
development programs may not support approval of the company's
triple combination regimens due to safety, efficacy or other
reasons, and (iii) 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)
1 CFQ-R results reported are based on a mixed effect model not
adjusted for baseline CFQ-R
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Vertex Pharmaceuticals
IncorporatedInvestors:Michael Partridge,
617-341-6108orEric Rojas, 617-961-7205orZach Barber,
617-341-6470orMedia:mediainfo@vrtx.comorNorth America:Megan
Goulart, + 1-617-341-6992orEurope & Australia:Rebecca
Hunt, +44 7718 962 690
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