-Study met primary safety endpoint and showed
improvements across multiple endpoints, including measures of
pancreatic function-
-Potential to modify the course of CF in
children as young as one year of age-
-Results support FDA and EMA filings in the
first quarter of 2018-
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced positive results from an open-label Phase 3 study of
KALYDECO® (ivacaftor) in children with cystic fibrosis (CF) ages 1
to 2 years who have one of 10 mutations in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene. The ARRIVAL study
met its primary endpoint of safety, showing that ivacaftor was
generally well tolerated, and safety data were consistent with
those seen in previous Phase 3 studies of ivacaftor in children
ages 2 to 5 years and 6 to 11 years. There was also a substantial
improvement in sweat chloride, a secondary endpoint, as well as in
multiple exploratory endpoints evaluating pancreatic function.
These data suggest the potential to modify the course of CF in
children as young as one year of age. The study is ongoing in
infants younger than one year old. Based on these results, Vertex
plans to submit applications for ivacaftor in children ages 1 to 2
years to the U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMA) in the first quarter of 2018.
“We know that cystic fibrosis is a progressive disease with
organ damage already present at birth, so the earlier patients can
begin treatment, the greater their potential for improved
outcomes,” said Jane Davies, M.D., Royal Brompton Hospital and
Imperial College, London, co-lead investigator of the ARRIVAL
study. “These results are incredibly exciting: they suggest that we
can begin treating the underlying cause of cystic fibrosis with
KALYDECO in children as young as one year of age.”
“We have a significant body of evidence demonstrating KALYDECO’s
immediate and long-term benefits and its potential to modify the
course of CF,” said Jeffrey Chodakewitz, M.D., Executive Vice
President and Chief Medical Officer at Vertex. “These results are
an important step in our goal of treating children as early as
possible to intervene in this progressive disease.”
KALYDECO is currently approved by the FDA for the treatment
of CF in patients ages 2 and older who have one of 38
ivacaftor-responsive mutations in the CFTR gene.
About the ARRIVAL Study
ARRIVAL is an ongoing 2-part, open-label Phase 3 study assessing
ivacaftor in children with CF younger than 2 years of age who have
one of the following ten mutations in the CFTR gene: G551D, G178R,
S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H. Part
A of the study is evaluating the safety and pharmacokinetics of
ivacaftor for five days to support the evaluation of ivacaftor for
24 weeks in Part B of the study. Part B is evaluating the safety,
pharmacokinetics and efficacy of ivacaftor for 24 weeks. The
primary endpoint of Part B of the study is safety, and secondary
endpoints include pharmacokinetics and absolute change in sweat
chloride. There are several exploratory endpoints, including ones
evaluating pancreatic function. Data reported today are from Part B
of the study in children ages 1 to 2 years; Parts A and B of the
study in infants younger than one year old are ongoing. Of the 18
children who completed Part B of the 24-week study, 17 enrolled in
a rollover study to continue receiving ivacaftor treatment. The
only participant not to continue in the rollover study was older
than 2 years of age, so elected to begin treatment with commercial
ivacaftor.
Key results from Part B of the ARRIVAL study in children ages 1
to 2 (n=19) are below.
Safety: The study met its primary endpoint of safety.
Safety data from this interim analysis were consistent with those
observed in previous Phase 3 studies in children ages 2 to 5 years
and 6 to 11 years. Ivacaftor was generally well tolerated through
24 weeks of treatment and the majority of adverse events were mild
or moderate in severity. No patients discontinued treatment due to
adverse events. The most common adverse events (≥30%) were cough,
pyrexia (fever), elevated liver enzymes and rhinorrhea (runny
nose). Serious adverse events were reported in two patients; one
patient had cough that was treated with IV antibiotics and one
patient had a viral infection followed by distal intestinal
obstruction syndrome and constipation. Two different patients
experienced elevated liver enzymes of greater than eight times the
upper limit of normal. Both patients had concurrent illnesses
during these elevations; upon subsequently resuming ivacaftor
treatment neither patient experienced any further elevations.
Sweat Chloride: Elevated sweat chloride levels are a
diagnostic hallmark in CF and are the result of CFTR protein
dysfunction. A reduction in sweat chloride is considered to be a
marker of improved CFTR function. People with CF typically have
elevated sweat chloride levels in excess of 60 mmol/L, while normal
values are typically less than 30-40 mmol/L.
In Part B of the ARRIVAL study in children ages 1 to 2 years,
the baseline sweat chloride level was 104.1 mmol/L (n=14). There
was a mean absolute decrease of -73.5 mmol/L (n=10) in sweat
chloride levels at 24 weeks of ivacaftor treatment; the median
sweat chloride level at the end of the study was 31.5 mmol/L
(n=14).
Pancreatic Function: In children with CF, pancreatic
insufficiency is one of the most significant clinical
manifestations of the disease. Pancreatic insufficiency is also the
most common gastrointestinal complication of CF. There are several
ways of evaluating pancreatic function in CF. Low levels, or the
complete absence, of elastase in the stool (known as fecal
elastase) are suggestive of pancreatic insufficiency; normal levels
of fecal elastase are above 200 µg/g. High levels of a chemical
made by the pancreas called immunoreactive trypsinogen (IRT) are
suggestive of pancreatic obstruction. High levels of the pancreatic
enzymes lipase and amylase are suggestive of pancreatitis, a known
complication of CF, which can lead to progressive pancreatic
damage.
In Part B of the ARRIVAL study in children ages 1 to 2 years,
the baseline fecal elastase level was 182.2 µg/g (n=19). There was
a mean absolute improvement in fecal elastase of 164.7 µg/g, which
was an exploratory endpoint, at 24 weeks of the study; the median
fecal elastase level at the end of the study was 357.0 µg/g (n=15).
There were also decreases in the exploratory endpoint of IRT and in
the safety assessments of lipase and amylase, which suggest
improvement in pancreatic sufficiency and early pancreatic
benefit.
Full results from the study will be submitted for presentation
at an upcoming medical conference.
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 protein 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 granules 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) INDICATION AND IMPORTANT
SAFETY INFORMATION
KALYDECO® (ivacaftor) is a prescription medicine used for the
treatment of cystic fibrosis (CF) in patients age 2 years 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 2 years 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 Prescribing Information for
KALYDECO.
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 and VX-659 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 second and
third paragraphs and statements regarding the expected timing of
regulatory applications to be submitted to the FDA and EMA. 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, (i) that the initial results set forth in this
press release may differ from the final results from this ongoing
study, (ii) that regulatory authorities may not approve, or approve
on a timely basis, ivacaftor in these patient populations due to
safety, efficacy or other reasons, and (iii) 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:mediainfo@vrtx.comorNorth America:Megan
Goulart, + 1-617-341-6992orEurope & Australia:Rebecca
Hunt, +44 7718 962 690
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