- Phase 2 data showed mean absolute
improvements in ppFEV1 of up to 13.3 and 13.8 percentage points for
VX-659 and VX-445, respectively, in triple combination with
tezacaftor and ivacaftor in people with CF who have one F508del
mutation and one minimal function mutation (F508del/Min); triple
combination regimens were generally well tolerated across the
studies -
- Regulatory discussions ongoing to finalize
design of Phase 3 programs; first program to begin in first half of
2018 -
NOTE: In the prior version of this press release, the dose of
tezacaftor was indicated as “q12h” in two places. The dose of
tezacaftor used in all dose arms was “QD” and the release has been
updated accordingly.
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced the selection of two next-generation correctors, VX-659
and VX-445, to advance into Phase 3 development as part of two
different triple combination regimens for people with cystic
fibrosis (CF). The decision to advance VX-659 and VX-445 into Phase
3 development was based on initial Phase 2 data, including new data
from ongoing Phase 2 studies that showed mean absolute improvements
in percent predicted forced expiratory volume in one second
(ppFEV1) of up to 13.3 and 13.8 percentage points from baseline
through four weeks of treatment for the triple combination regimens
with VX-659 (400mg QD) or VX-445 (200mg QD), respectively, in
people who have one F508del mutation and one minimal function
mutation (F508del/Min). Regulatory discussions are ongoing to
finalize the design of Phase 3 programs for VX-659 and VX-445. Upon
completion of these discussions, Vertex plans to initiate a Phase 3
program in the first half of 2018 to evaluate VX-659 in triple
combination with tezacaftor and ivacaftor. In addition, the company
plans to initiate a Phase 3 program in mid-2018 to evaluate VX-445
in triple combination with tezacaftor and VX-561 as a once-daily
regimen, pending additional data in the first half of 2018,
including the Phase 2 data on the combination of VX-445, tezacaftor
and VX-561. Vertex will discuss the Phase 2 data and Phase 3
development strategy during the company’s fourth-quarter and
full-year 2017 financial results call for investors today, January
31, 2018 at 4:30 p.m. ET.
The triple combination regimens were generally well tolerated
across both studies, and the majority of adverse events were mild
to moderate in severity. Across the studies, the discontinuation
rate due to adverse events was low.
“These results support the selection of both the VX-659 and
VX-445 triple combination regimens and underscore the potential for
these regimens to provide significant clinical benefits for up to
90 percent of people with CF,” said Jeffrey Chodakewitz, M.D.,
Executive Vice President and Chief Medical Officer at Vertex. “We
look forward to concluding our discussions with regulators and
initiating Phase 3 development in the first half of the year, with
the goal of bringing a triple combination regimen to patients as
quickly as possible.”
“The triple combination data demonstrate the rapid advances we
are making in treating the underlying cause of CF,” said Jennifer
Taylor-Cousar, M.D., M.S.C.S., Associate Professor of Medicine and
Pediatrics at National Jewish Health, Colorado, and co-chair of
Vertex’s Triple Combination Steering Committee. “Together, all the
Phase 2 data to date provide further evidence that the addition of
a next-generation corrector to tezacaftor and ivacaftor has the
potential to provide substantial clinical benefits to patients with
one F508del and one minimal function mutation who don’t currently
have a medicine to treat the underlying cause of their CF, as well
as to provide additional benefits to patients with at least one
F508del mutation who are already eligible for CFTR modulator
therapies.”
About the Phase 3 Programs
Vertex is in the process of finalizing Phase 3 study designs for
VX-659 and VX-445 with regulatory agencies, with the goal of
bringing a potential triple combination regimen to patients as
quickly as possible. Upon completion of these discussions, the
company plans to begin the first Phase 3 program in the first half
of 2018, which will initially evaluate VX-659 in triple combination
with tezacaftor and ivacaftor in F508del/Min patients. A second
study, also to begin in the first half of 2018, will evaluate this
triple combination in people with two copies of the F508del
mutation (F508del/F508del). Pending data from the ongoing Phase 2
study and completion of regulatory discussions, Vertex plans to
initiate a Phase 3 program in mid-2018 to evaluate VX-445 with
tezacaftor and VX-561 as a once-daily regimen in F508del/Min and
F508del/F508del patients.
The VX-659 and VX-445 Phase 2 studies are both ongoing to
evaluate triple combination regimens with tezacaftor and ivacaftor
in F508del/F508del patients and triple combination regimens with
tezacaftor and VX-561 as a once-daily regimen in F508del/Min
patients. Vertex expects these data in the first half of 2018.
The decision to advance VX-659 and VX-445 into Phase 3
development was based on initial data from the Phase 2 studies of
the company’s four next-generation correctors – VX-659, VX-445,
VX-152 and VX-440, each in triple combination with tezacaftor and
ivacaftor. Initial data from the ongoing VX-659 and VX-445 studies
were announced today and are below. In July 2017, Vertex reported
results from the VX-440 study as well as results from the 100mg and
200mg arms of the VX-152 study.
About the VX-659 Phase 2 Study
This ongoing randomized, double-blind Phase 2 study is
evaluating VX-659 (80mg, 240mg and 400mg QD) in combination with
tezacaftor and ivacaftor in two different groups of people with CF
ages 18 and older – those who have one F508del mutation and one
minimal function mutation (Part 1), and in those who have two
copies of the F508del mutation (Part 2). Minimal function mutations
are those that result in little-to-no functioning CFTR protein and
are not responsive to ivacaftor, tezacaftor or the combination of
tezacaftor and ivacaftor. Part 3 of the study is evaluating VX-659
in combination with tezacaftor and VX-561 as a potential once-daily
triple combination regimen in F508del/Min patients. The primary
objectives of the study are safety, tolerability and efficacy as
assessed by mean absolute change in ppFEV1 from baseline. Secondary
endpoints include change in sweat chloride and Cystic Fibrosis
Questionnaire-Revised (CFQ-R). Data reported today are from Part 1
of the study. Parts 2 and 3 of the study are ongoing with data
expected in the first half of 2018.
Safety Data: In Part 1 of the study, the triple
combination regimen was generally well tolerated. The majority of
adverse events were mild or moderate. Serious adverse events were
reported in seven patients: three patients in the placebo group (2
with infective pulmonary exacerbations and 1 with decreased
pulmonary function test) and four in the triple combination groups
(3 with infective pulmonary exacerbations and 1 with influenza).
None of these serious adverse events were considered related to
treatment and none resulted in treatment discontinuation. The most
common adverse events (>10%), regardless of treatment group,
were cough, headache, oropharyngeal (throat) pain and sputum
increased. There were no discontinuations due to adverse events.
One patient interrupted treatment due to an adverse event in the
triple combination treatment groups (rash). The rash resolved
following interruption of treatment and the patient subsequently
restarted and completed triple combination treatment without any
further incidence.
Efficacy Data: Part 1 of the study evaluated the triple
combination for four weeks in 63 patients who have one F508del
mutation and one minimal function mutation (10 in placebo, 11 in
VX-659 80mg, 20 in VX-659 240mg and 22 in VX-659 400mg). A summary
of the within-group lung function and sweat chloride data is
provided below:
VX-659 in F508del/Min Patients
Mean Absolute Within-GroupChange
From Baseline Through Day 29*
Mean Absolute Within-Group Change in
ppFEV1 (percentage points)
Mean Absolute Within-Group Change in Sweat Chloride (mmol/L)
Triple placebo +0.3
(p=0.9053)
+2.9
(p=0.5338)
VX-659 (80mg QD) + tezacaftor (100mg QD) + ivacaftor (150mg q12h)
+10.2
(p=0.0004)
-45.8
(p<0.0001)
VX-659 (240mg QD) + tezacaftor (100mg QD) + ivacaftor (150mg q12h)
+11.6
(p<0.0001)
-43.7
(p<0.0001)
VX-659 (400mg QD) + tezacaftor (100mg QD) + ivacaftor (150mg q12h)
+13.3
(p<0.0001)
-51.4
(p<0.0001)
* all p-values are within group p-values
based on mixed effect models; values expressed as ‘Through Day 29'
are the average of Day 15 and Day 29 measures
A secondary endpoint in the study measured mean absolute change
in the respiratory domain of CFQ-R,1 a validated patient-reported
outcome measure, at Day 29. The mean absolute improvements for
patients who received the triple combination were 24.6 points
(VX-659 80mg), 19.8 points (VX-659 240mg) and 21.8 points (VX-659
400mg). The improvement for those who received placebo was 4.7
points.
About the VX-445 Phase 2 Study
This ongoing Phase 2 randomized, double-blind study evaluated
the safety and tolerability of single and multiple ascending doses
of VX-445 alone and in triple combination with tezacaftor and
ivacaftor in healthy volunteers (Parts A, B and C). It is also
evaluating the safety, tolerability and efficacy of VX-445 (50mg,
100mg and 200mg QD) in triple combination with tezacaftor and
ivacaftor for four weeks in people with CF ages 18 and older who
have one F508del mutation and one minimal function mutation (Part
D) and in people who have two copies of the F508del mutation (Part
E). Part F of the study is evaluating VX-445 in combination with
tezacaftor and VX-561 as a potential once-daily triple combination
regimen in F508del/Min patients. The primary objectives of the
parts of the study in CF patients are safety, tolerability and
efficacy as assessed by mean absolute change in ppFEV1 from
baseline. Secondary endpoints include change in sweat chloride and
CFQ-R. Data reported today are from Part D of the study. Parts E
and F of the study are ongoing with data expected in the first half
of 2018.
Safety Data: In Part D of the study, the triple
combination regimen was generally well tolerated. The majority of
adverse events were mild or moderate. Serious adverse events were
reported in five patients: two patients in the placebo group (1
with hemoptysis and 1 with infective pulmonary exacerbation) and
three patients in the triple combination groups (1 patient with
infective pulmonary exacerbation, jugular vein thrombosis related
to a central line, and distal intestinal obstruction syndrome; 1
patient with infective pulmonary exacerbation and influenza; and 1
patient with infective pulmonary exacerbation). None of these
serious adverse events were considered related to treatment and
none resulted in treatment discontinuation. The most common adverse
events (>10%), regardless of treatment group, were cough, sputum
increased, infective pulmonary exacerbation, hemoptysis, headache,
nasal congestion, nausea, oropharyngeal pain and pyrexia. Two
patients discontinued treatment due to adverse events in the triple
combination treatment groups (1 patient with rash and 1 patient
with increased bilirubin without associated elevations in
transaminases) and none in the placebo group. Following treatment
discontinuation, the rash resolved and the increased bilirubin
returned to baseline. Two patients interrupted treatment due to
adverse events in the triple combination groups (1 with
constipation and 1 with increased bilirubin without associated
elevations in transaminases); both events resolved when treatment
was interrupted and both patients subsequently restarted and
completed triple combination treatment without further
incident.
Efficacy Data: Part D of the study evaluated the triple
combination for four weeks in 65 patients who have one F508del
mutation and one minimal function mutation (12 in combined placebo,
10 in VX-445 50mg, 22 in VX-445 100mg and 21 in VX-445 200mg). A
summary of the within-group lung function and sweat chloride data
is provided below:
VX-445 in F508del/Min Patients
Mean Absolute Within-GroupChange
From Baseline Through Day 29*
Mean Absolute Within-Group
Change in ppFEV1(percentage points)
Mean Absolute Within-Group
Change in Sweat Chloride (mmol/L)
Triple placebo 0.0
(p=0.9943)
-2.2
(p=0.5804)
VX-445 (50mg QD) + tezacaftor(100mg QD) +
ivacaftor (150mg q12h)
+11.1
(p<0.0001)
-38.2
(p<0.0001)
VX-445 (100mg QD) + tezacaftor(100mg QD) +
ivacaftor (150mg q12h)
+7.8
(p<0.0001)
-33.2
(p<0.0001)
VX-445 (200mg QD) + tezacaftor(100mg QD) +
ivacaftor (150mg q12h)
+13.8
(p<0.0001)
-39.1
(p<0.0001)
* all p-values are within group p-values
based on mixed effect models; values expressed as ‘Through Day 29'
are the average of Day 15 and Day 29 measures
A secondary endpoint in the study measured mean absolute change
in the respiratory domain of CFQ-R at Day 29. The mean absolute
improvements for patients who received the triple combination were
20.8 points (VX-445 50mg), 15.4 points (VX-445 100mg) and 25.7
points (VX-445 200mg). The improvement for those who received
placebo was 4.2 points.
About the VX-152 Phase 2 Study
In July 2017, Vertex reported results for the 100mg and 200mg
dose arms of the ongoing VX-152 Phase 2 study, which was also
evaluating a 300mg dose of VX-152 in combination with tezacaftor
and ivacaftor for two weeks in people who have one F508del mutation
and one minimal function mutation and for four weeks in people who
have two copies of the F508del mutation. Results from the 300mg
arms of the VX-152 study were consistent with previously reported
results, which showed a favorable safety profile, and rapid and
significant increases in ppFEV1.
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
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), tezacaftor, 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 and Dr.
Taylor-Cousar’s statements in the third and fourth paragraphs,
respectively, and the information provided regarding (i) Vertex's
selection of VX-659 and VX-445, (ii) additional data Vertex expects
from its ongoing Phase 2 next-generation clinical trials, (iii)
Vertex’s regulatory discussions to finalize the design of the Phase
3 development programs and (iv) the timing and design of Vertex’s
Phase 3 development programs for VX-659 and VX-445. 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 development programs to evaluate VX-659 and/or VX-445
as part of triple combination regimens, (ii) that the data set
forth in this press release from the ongoing Phase 2 clinical
trials may differ from data from additional parts of these Phase 2
clinical trials, (iii) 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 (iv) 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
View source
version on businesswire.com: http://www.businesswire.com/news/home/20180131006482/en/
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
Vertex Pharmaceuticals (NASDAQ:VRTX)
Historical Stock Chart
From Apr 2024 to May 2024
Vertex Pharmaceuticals (NASDAQ:VRTX)
Historical Stock Chart
From May 2023 to May 2024