Market Overview

Vertex Announces Positive Results from Open-Label Phase 3 Study of KALYDECO® (ivacaftor) in Children with Cystic Fibrosis Ages 1 to 2 Years


-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-

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

"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) 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
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

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
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.


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