- Phase 2 results of VX-659 and VX-445 triple
combination regimens concurrently published in The New England
Journal of Medicine -
- Phase 3 ARRIVAL data support treating the
underlying cause of cystic fibrosis with KALYDECO® (ivacaftor) as
early as six months of age -
- Patient-reported outcomes data from Phase 3
EVOLVE and EXPAND studies continue to support the clinical benefit
of SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) -
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced that eight scientific abstracts from the company’s
portfolio of cystic fibrosis (CF) medicines are being presented at
the 32nd North American Cystic Fibrosis Conference taking place
October 18-20, 2018 in Denver.
Key highlights include presentations of Phase 2 data evaluating
clinical safety and efficacy as well as in vitro data of two triple
combination regimens (VX-659, tezacaftor and ivacaftor; VX-445,
tezacaftor and ivacaftor) in patients with one F508del mutation and
one minimal function mutation (F508del/Min) and in patients with
two F508del mutations (F508del/F508del), as well as in once-daily
triple combination regimens (VX-659, tezacaftor and VX-561; VX-445,
tezacaftor and VX-561) in F508del/Min patients. Data from these
studies were also published online today in The New England Journal
of Medicine (NEJM).
Phase 3 KALYDECO® (ivacaftor) data from ARRIVAL, the first study
of KALYDECO in infants six to <12 months old with a cystic
fibrosis transmembrane conductance regulator (CFTR) gating or R117H
mutation is also being presented.
“The data we are presenting at this year’s Conference reinforce
our belief that treating the underlying cause of CF early in life
may modify the course of this disease, and demonstrate the rapid
progress we are making toward our goal of developing a single
medicine that will treat the underlying cause of CF in up to 90
percent of people with this devastating disease,” said Reshma
Kewalramani, M.D., Executive Vice President and Chief Medical
Officer at Vertex.
Presentation highlights include:
VX-659/Tezacaftor/Ivacaftor – Phase 2 Triple Combination
Results
“Preliminary safety and efficacy of the triple combination CFTR
modulator regimen VX-659/TEZ/IVA in CF.” Poster 216 during Thematic
Poster Session 01--CLIN-NT: Clinical Care in the Era of CFTR
Modulators on Thursday, October 18 from 9:45 AM to 11:05 AM MT
This Phase 2 randomized, double-blind study assessed VX-659 in
combination with tezacaftor and ivacaftor for 4 weeks in people
with CF ages 18 and older with either F508del/Min or
F508del/F508del mutations, and in combination with tezacaftor and
VX-561 in patients with CF ages 18 and older with F508del/Min
mutations. Primary endpoints included safety and tolerability, as
well as efficacy measured by mean absolute change in percent
predicted forced expiratory volume in one second (ppFEV1) from
baseline. Secondary endpoints included change in sweat chloride
(SwCl) and Cystic Fibrosis Questionnaire-Revised Respiratory Domain
score (CFQ-R RD).
The study met its primary endpoint and showed that treatment
with the triple combination regimen resulted in statistically
significant and clinically meaningful increases in lung function,
as well as improvements in sweat chloride and CFQ-R RD. The
improvements in the F508del/F508del patients were observed when
VX-659 was added in people already receiving tezacaftor/ivacaftor.
Most adverse events (AEs) were mild to moderate in severity. The
most common AEs in this group were cough, infective pulmonary
exacerbation of cystic fibrosis, headache, oropharyngeal pain and
sputum increased.
The Phase 3 ECLIPSE clinical trial program assessing
VX-659/tezacaftor/ivacaftor in people with CF with F508del/Min, who
today don’t have a medicine to treat the underlying cause of their
disease, or F508del/F508del mutations is currently ongoing.
"Since the discovery of CFTR modulators, we have envisioned
highly effective CFTR modulation therapy that could modify the
progression of the disease for all CF patients,” said Steven M.
Rowe, M.D., M.S.P.H., co-chair of Vertex's Triple Combination
Steering Committee and Director of the Cystic Fibrosis Research
Center at the University of Alabama at Birmingham. “These
impressive results showing marked improvements in lung function and
a substantial reduction in sweat chloride in patients with one or
two F508del mutations demonstrate we are an important step closer
towards achieving that goal.”
VX-445/Tezacaftor/Ivacaftor – Phase 2 Triple Combination
Results
“Preliminary safety and efficacy of the triple-combination CFTR
modulator regimen VX-445/TEZ/IVA in CF.” Poster 213 during Thematic
Poster Session 01--CLIN-NT: Clinical Care in the Era of CFTR
Modulators on Thursday, October 18 from 9:45 AM to 11:05 AM MT
This Phase 2, randomized, double-blind study assessed VX-445 in
combination with tezacaftor and ivacaftor for 4 weeks in people
with CF ages 18 and older with F508del/Min or F508del/F508del
mutations, and in combination with tezacaftor and VX-561 in
patients with CF ages 18 and older with F508del/Min mutations.
Primary endpoints included safety and tolerability, as well as
efficacy measured by mean absolute change in ppFEV1 from baseline.
Secondary endpoints included change in SwCl and CFQ-R RD.
The study met its primary endpoint and showed that treatment
with the triple combination regimen resulted in statistically
significant and clinically meaningful increases in lung function,
as well as improvements in sweat chloride and CFQ-R RD. The
improvements in the F508del/F508del patients were observed when
VX-445 was added in people already receiving tezacaftor/ivacaftor.
Most adverse events (AEs) were mild to moderate in severity. The
most common AEs include cough, sputum increased, infective
pulmonary exacerbation of cystic fibrosis, hemoptysis and
pyrexia.
The Phase 3 AURORA clinical trial program assessing
VX-445/tezacaftor/ivacaftor in people with CF with F508del/Min, who
today don’t have a medicine to treat the underlying cause of their
disease, or F508del/F508del mutations is ongoing.
“The results from these two studies are truly exciting because
they represent the potential for these regimens to provide
significant clinical benefits for even more people with CF,” said
Jennifer Taylor-Cousar, M.D., co-chair of Vertex's Triple
Combination Steering Committee and Associate Professor, Departments
of Medicine and Pediatrics, Pulmonary Divisions, Medical Director
of Clinical Research Services and Co-Director and Director of the
CF Therapeutics Development Network, Adult CF Program, National
Jewish Health, Colorado.
KALYDECO – Results from the Phase 3 ARRIVAL Study in Infants
aged Six to <12 Months
“Ivacaftor Treatment In Patients 6 To < 12 Months Old With A
CFTR Gating Mutation: Results Of A Phase 3, Two-Part Single Arm
Study.” Poster 810 during Poster Session on Thursday, October 18
from 11:15 AM to 1:45 PM MT
Results from the ongoing, open-label, Phase 3 ARRIVAL study of
17 infants with CF aged six to <12 months who have a CFTR gating
(G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D)
or R117H mutation showed treatment with KALYDECO for 24 weeks was
generally safe and well tolerated and resulted in substantial
improvements in sweat chloride, which was a secondary endpoint,
indicating improved CFTR function. Additionally, patients treated
with KALYDECO had increases in fecal elastase and reductions in
immunoreactive trypsin/trypsinogen, lipase and amylase levels,
which were exploratory endpoints, suggesting a pancreatic benefit
early in life.
A total of 11 patients enrolled in the 24-week safety portion of
the study, with a mean sweat chloride of 101.5 mmol/L at baseline.
Following 24 weeks of treatment with KALYDECO, the safety profile
was consistent with that observed in previous Phase 3 studies of
older children and adults. Most AEs were mild to moderate in
severity, and no patients discontinued treatment due to AEs. The
most common AE (7/11 patients, 63.6%) was cough. SAEs (viral
respiratory tract infection, viral rash and cough) occurred in
three out of 11 patients and were assessed as not related or
unlikely related to treatment with KALYDECO. The mean sweat
chloride level was reduced by 58.6 mmol/L to 43.1 mmol/L for the
six patients with both baseline and Week 24 sweat chloride
measurements. Sweat chloride is used as a tool to diagnose CF,
where levels greater than or equal to 60 mmol/L indicate that CF is
likely, levels of 30-59 mmol/L indicate CF is possible and levels
less than 30 indicate that CF is unlikely.
The study is ongoing in infants younger than six months old.
These data support Vertex’s planned submissions to the U.S. Food
and Drug Administration (FDA) and European Medicines Agency (EMA)
for KALYDECO in children aged 6 to <12 months later this
year.
Additional Presentations
In addition to the studies noted above, other presentations at
NACFC include:
- EVOLVE AND EXPAND PATIENT-REPORTED
OUTCOMES (PRO): Data were reported on PRO analyses of
tezacaftor/ivacaftor treatment from the Phase 3 EVOLVE and EXPAND
studies. The two randomized, double-blind, placebo-controlled
trials in patients 12 years and older resulted in patient-reported
improvements in outcomes beyond respiratory symptoms, including
health perceptions and physical functioning, further supporting the
value of tezacaftor/ivacaftor treatment in patients with CF with
F508del/F508del mutations or with one F508del mutation and one
residual function mutation (F508del/RF). (Poster 308 and 309)
- EVOLVE, EXPAND, EXTEND RETROSPECTIVE
ANALYSIS: Researchers conducted a retrospective analysis of
Phase 3 studies assessing tezacaftor/ivacaftor in patients 12 years
or older with CF with F508del/F508del mutations (EVOLVE) and in
those with an F508del/RF mutation (EXPAND, which also assessed
ivacaftor), as well as in an ongoing open-label extension study
(EXTEND). Results indicated that treatment with
tezacaftor/ivacaftor improves lung function in F508del/F508del and
F508del/RF patients by reducing airway resistance and improving
breathing capacity. (Poster 135)
- BRIO INTERIM RESULTS: BRIO is an
ongoing observational, non-interventional, multi-center study in
patients with CF treated with KALYDECO in the conditions of a
real-world setting in France. Findings from the 12-month interim
analysis in patients six years and older demonstrated that the
real-world effectiveness of KALYDECO in France is consistent with
results from Phase 3 trials, including improvement in ppFEV1, body
mass index (BMI) and rate of pulmonary exacerbations (PEx). (Poster
34)
- KALYDECO REAL-WORLD ANALYSIS: A
five-year, real-world analysis of subgroups of pediatric,
adolescent and adult patients treated with KALYDECO from the U.S.
Cystic Fibrosis Registry found no new safety concerns and
consistent clinical benefits relative to comparators, continuing to
support disease modification with the treatment. (Poster 22)
About Cystic Fibrosis
Cystic fibrosis 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 KALYDECO® (ivacaftor)
KALYDECO (ivacaftor) is the first medicine to treat the
underlying cause of CF in people with specific mutations in the
CFTR gene. Known as a CFTR potentiator, KALYDECO is an oral
medicine designed to keep CFTR proteins at the cell surface open
longer to improve the transport of salt and water across the cell
membrane, which helps hydrate and clear mucus from the airways.
KALYDECO is available as 150 mg tablets for adults and pediatric
patients age 6 years and older, and is taken with fat-containing
food. It is also available as 50 mg and 75 mg oral granules for
weight-based dosing in pediatric patients ages 2 to less than 6
years and is administered with soft-food or liquid with
fat-containing food.
People with CF who have specific mutations in the CFTR gene are
currently benefiting from KALYDECO in 27 different countries across
North America, Europe and Australia.
KALYDECO® (ivacaftor) U.S. INDICATION AND
IMPORTANT SAFETY INFORMATION
KALYDECO (ivacaftor) is a prescription medicine used for the
treatment of cystic fibrosis (CF) in patients age 12 months and
older who have at least one mutation in their CF gene that is
responsive to KALYDECO. Patients should talk to their doctor to
learn if they have an indicated CF gene mutation. It is not known
if KALYDECO is safe and effective in children under 12 months of
age.
Patients should not take KALYDECO if they are taking certain
medicines or herbal supplements such as: the antibiotics
rifampin or rifabutin; seizure medications such as phenobarbital,
carbamazepine, or phenytoin; or St. John's wort.
Before taking KALYDECO, patients should tell their doctor if
they: have liver or kidney problems; drink grapefruit juice, or
eat grapefruit or Seville oranges; are pregnant or plan to become
pregnant because it is not known if KALYDECO will harm an unborn
baby; and are breastfeeding or planning to breastfeed because is
not known if KALYDECO passes into breast milk.
KALYDECO may affect the way other medicines work, and other
medicines may affect how KALYDECO works. Therefore the dose of
KALYDECO may need to be adjusted when taken with certain
medications. Patients should especially tell their doctor if they
take antifungal medications such as ketoconazole, itraconazole,
posaconazole, voriconazole, or fluconazole; or antibiotics such as
telithromycin, clarithromycin, or erythromycin.
KALYDECO can cause dizziness in some people who take it.
Patients should not drive a car, use machinery, or do anything that
needs them to be alert until they know how KALYDECO affects them.
Patients should avoid food containing grapefruit or Seville
oranges while taking KALYDECO.
KALYDECO can cause serious side effects including:
High liver enzymes in the blood have been reported in
patients receiving KALYDECO. The patient's doctor will do blood
tests to check their liver before starting KALYDECO, every 3 months
during the first year of taking KALYDECO, and every year while
taking KALYDECO. For patients who have had high liver enzymes in
the past, the doctor may do blood tests to check the liver more
often. Patients should call their doctor right away if they have
any of the following symptoms of liver problems: pain or discomfort
in the upper right stomach (abdominal) area; yellowing of their
skin or the white part of their eyes; loss of appetite; nausea or
vomiting; or dark, amber-colored urine.
Abnormality of the eye lens (cataract) has been noted in
some children and adolescents receiving KALYDECO. The patient's
doctor should perform eye examinations prior to and during
treatment with KALYDECO to look for cataracts. The most common side
effects include headache; upper respiratory tract infection (common
cold), which includes sore throat, nasal or sinus congestion, and
runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and
dizziness.
These are not all the possible side effects of KALYDECO.
Please click here to see the full U.S.
Prescribing Information for KALYDECO.
About SYMDEKO® (tezacaftor/ivacaftor and
ivacaftor)
Some mutations result in CFTR protein that is not processed or
folded normally within the cell, and that generally does not reach
the cell surface. SYMDEKO is a combination of tezacaftor and
ivacaftor. Tezacaftor is designed to address the trafficking and
processing defect of the CFTR protein to enable it to reach the
cell surface where ivacaftor can increase the amount of time the
protein stays open.
U.S. INDICATION AND IMPORTANT SAFETY INFORMATION FOR
SYMDEKO® (tezacaftor/ivacaftor and ivacaftor)
tablets
SYMDEKO is a prescription medicine used for the treatment of
cystic fibrosis (CF) in patients aged 12 years and older who have
two copies of the F508del mutation, or who have at least one
mutation in the CF gene that is responsive to treatment with
SYMDEKO. Patients should talk to their doctor to learn if they have
an indicated CF gene mutation. It is not known if SYMDEKO is safe
and effective in children under 12 years of age.
Patients should not take SYMDEKO if they take certain
medicines or herbal supplements such as: the antibiotics
rifampin or rifabutin; seizure medicines such as phenobarbital,
carbamazepine, or phenytoin; St. John's wort.
Before taking SYMDEKO, patients should tell their doctor if
they: have or have had liver problems; have kidney problems;
are pregnant or plan to become pregnant because it is not known if
SYMDEKO will harm an unborn baby; are breastfeeding or planning to
breastfeed because it is not known if SYMDEKO passes into breast
milk.
SYMDEKO may affect the way other medicines work, and other
medicines may affect how SYMDEKO works. Therefore, the dose of
SYMDEKO may need to be adjusted when taken with certain medicines.
Patients should especially tell their doctor if they take
antifungal medicines such as ketoconazole, itraconazole,
posaconazole, voriconazole, or fluconazole; or antibiotics such as
telithromycin, clarithromycin, or erythromycin.
SYMDEKO may cause dizziness in some people who take it.
Patients should not drive a car, use machinery, or do anything that
requires alertness until they know how SYMDEKO affects them.
Patients should avoid food or drink that contains
grapefruit or Seville oranges while they are taking SYMDEKO.
SYMDEKO can cause serious side effects, including:
High liver enzymes in the blood, which have been reported
in people treated with SYMDEKO or treated with ivacaftor alone. The
patient's doctor will do blood tests to check their liver before
they start SYMDEKO, every 3 months during the first year of taking
SYMDEKO, and every year while taking SYMDEKO. Patients should call
their doctor right away if they have any of the following symptoms
of liver problems: pain or discomfort in the upper right stomach
(abdominal) area; yellowing of the skin or the white part of the
eyes; loss of appetite; nausea or vomiting; dark, amber-colored
urine.
Abnormality of the eye lens (cataract) in some children
and adolescents treated with SYMDEKO or with ivacaftor alone. If
the patient is a child or adolescent, their doctor should perform
eye examinations before and during treatment with SYMDEKO to look
for cataracts.
The most common side effects of SYMDEKO include headache,
nausea, sinus congestion, and dizziness.
These are not all the possible side effects of SYMDEKO.
Please click here to see the full U.S.
Prescribing Information for SYMDEKO.
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 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), SYMDEKOTM
(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, the statements in the fourth, eighth
and twelfth paragraphs of the press release and statements
regarding (i) ongoing clinical trials, including the Phase 3
ECLIPSE trial, the Phase 3 AURORA trial and the Phase 3 ARRIVAL
trial in patients less than 6 months of age and (ii) planned
regulatory submissions to the FDA and EMA. While Vertex believes
the forward-looking statements contained in this press release are
accurate, 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 data from the company's development
programs may not support registration or further development of its
compounds 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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Vertex Pharmaceuticals IncorporatedInvestors:Michael
Partridge, 617-341-6108orEric Rojas, 617-961-7205orZach Barber,
617-341-6470orMedia:North America:Heather Nichols,
617-341-6992mediainfo@vrtx.comorEurope & Australia:Rebecca
Hunt, +44 7718 962 690
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