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Vertex Announces Presentations of Data at North American Cystic Fibrosis Conference that Demonstrate Important Progress Toward Goal of Helping All People with CF

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- Data from ongoing extension study of ORKAMBI®
(lumacaftor/ivacaftor) in children ages 6-11 and real-world KALYDECO
®
(ivacaftor) data demonstrate long-term safety and other benefits of
these medicines -

- New data from ongoing extension study of tezacaftor/ivacaftor
combination demonstrate sustained benefits up to 48 total weeks of
treatment -

- First presentation of previously announced early data from Phase 1
and Phase 2 studies of three different triple combination regimens -

Vertex
Pharmaceuticals Incorporated
(NASDAQ:VRTX) today announced
presentations of data at the Annual North American Cystic Fibrosis
Conference (NACFC), November 2 to 4, 2017, in Indianapolis, from across
the company's portfolio of cystic fibrosis (CF) medicines and medicines
in development that demonstrate important progress toward the company's
goal of helping all people with CF. Key presentations highlight the
acute and long-term benefits of CFTR modulation, including data from an
ongoing extension study of ORKAMBI® (lumacaftor/ivacaftor)
showing that improvements in lung function and other measures of disease
were maintained through 48 weeks in children with CF ages 6 to 11 who
have two copies of the F508del mutation, and real-world data
demonstrating the impact of KALYDECO® (ivacaftor) across
multiple CF measures in slowing disease progression. Also being
presented at the Conference are new data from an ongoing extension study
of the tezacaftor/ivacaftor combination demonstrating sustained benefits
for up to 48 total weeks of treatment, and the first presentation of
previously announced data from Phase 1 and Phase 2 studies of three
different triple combination regimens.

"The breadth of data presented at this meeting demonstrate significant
progress toward our key goals of bringing disease-modifying medicines to
all people with CF and increasing the benefits for patients on our
current medicines," said Jeffrey Chodakewitz, M.D., Executive Vice
President and Chief Medical Officer at Vertex. "We also know that many
people with CF are still waiting for a medicine to treat the cause of
their disease and we are continuing our efforts to develop additional
new medicines, such as triple combination regimens, for these people
with a sense of urgency."

ORKAMBI in Children Ages 6 to 11

"Safety and Efficacy of Lumacaftor/Ivacaftor (LUM/IVA) in Patients
aged ≥6 years with CF Homozygous for F508del-CFTR (Phase 3 Extension
Study)." Poster 278.

Two hundred and forty children ages 6 to 11 who have two copies of the F508del
mutation and who completed 24 weeks of treatment in either the Phase 3
randomized, double-blind, placebo-controlled ORKAMBI study (designed to
support approval in the EU) or the open-label Phase 3 ORKAMBI safety
study (designed to support approval in the U.S.) entered a Phase 3
rollover study to receive ORKAMBI for an additional 96 weeks. A
pre-planned interim analysis was conducted once all participants
completed 24 weeks in the rollover study for a total of 48 total weeks
of ORKAMBI treatment (48 weeks for those who received ORKAMBI in the
placebo-controlled study or in the open-label study; 24 weeks for those
who received placebo in the placebo-controlled study).

This analysis showed that the improvements over baseline in lung
function (measured by the absolute change in lung clearance index, or LCI2.5),
sweat chloride and body mass index (BMI) were maintained through 48
weeks of treatment. In addition, the pattern and magnitude of response
observed after the initiation of ORKAMBI in children who previously
received placebo were similar to those seen among children who received
ORKAMBI in the initial studies.

Safety data from this interim analysis were similar to those observed in
previous Phase 3 studies in children ages 6 to 11. Most adverse events
were mild or moderate. Six patients discontinued treatment due to
adverse events (3 due liver enzyme elevations, 1 due to autoimmune
hepatitis, 1 due to a gastrointestinal disorder and 1 due to urticaria
(hives)). The most common adverse events (≥15%) were cough, infective
pulmonary exacerbation, pyrexia (fever), nasal congestion, headache and
upper respiratory tract infection. Serious adverse events were reported
in 40 patients (17%). Predefined respiratory events were observed more
frequently in those who previously received placebo compared to those
who continued ORKAMBI treatment (19.8% vs 8.4%); all were mild or
moderate, and none led to treatment discontinuation. Six patients (2.5%)
experienced elevated liver enzymes of greater than eight times the upper
limit of normal. Of the three patients who discontinued treatment due to
elevated liver enzymes, all levels returned to baseline after stopping
treatment.

"Cystic fibrosis is a progressive disease where the damage begins at
birth," said Mark Chilvers, M.D., lead investigator for the rollover
study, BC Children's Hospital, Clinical Associate Professor, Division of
Respiratory Medicine, Department of Pediatrics, Faculty of Medicine,
University of British Columbia. "Because of this, it is critical to
begin treating the disease as early as possible. These data are
important because they demonstrate that in children as young as 6 years
of age, ORKAMBI is well tolerated and that the respiratory and
nutritional changes are sustained over time."

"Effect of Lumacaftor/Ivacaftor on Total, Bronchiectasis, and Air
Trapping Computed Tomography (CT) Scores in Children Homozygous for
F508del-CFTR: Exploratory Imaging Substudy." Poster 197. Oral
presentation during Workshop W18--NT: Innovative Approaches to CF
Therapy.

"Feasibility of Ultrashort Echo Time (UTE) MRI to Evaluate the Effect
of Lumacaftor/Ivacaftor Therapy in Children with Cystic Fibrosis (CF)
Homozygous for F508del." Poster 266.

CF-related lung disease is known to start before it is detectable by a
decrease in lung function as measured by percent predicted forced
expiratory volume in one second, or ppFEV1. Once ppFEV1
has fallen below normal, structural lung damage may have already
occurred; much of this can be irreversible.

This exploratory sub-study was conducted in 19 children with CF ages 6
to 11 who have two copies of the F508del mutation and who
participated in the Phase 3 ORKAMBI study designed to support EU
approval (n=206). An exploratory analysis of CT and MRI scans was used
to evaluate treatment effects in children with CF with mild lung
disease. In the 24-week exploratory analysis, treatment with ORKAMBI
showed positive trends toward improvement in Total Brody Score, which is
a system that evaluates the extent and severity of structural lung
damage. These results demonstrate the potential utility of CT and MRI
for monitoring the treatment effects of CFTR modulators.

KALYDECO Real-World Outcomes

"Real-World Outcomes in Patients with CF Treated with Ivacaftor: 2015
US and UK CF Registry Analyses." Poster 496.

"Disease Progression in Patients with CF Treated with Ivacaftor:
Analyses of Real-World Data from the US and UK CF Registries." Poster
497.

Interim data collected through 2015 from the ongoing, five-year,
post-approval observational safety study evaluating long-term outcomes
in CF patients on KALYDECO continue to support that treating the
underlying cause of CF has the potential to modify the course of disease
in a real-world setting.

In both the U.S. and UK registries, patients who received KALYDECO in
2015 had lower risk of death, transplantation, hospitalizations and
pulmonary exacerbations compared to patients who were matched on age,
gender and genotype class who did not receive KALYDECO. In addition,
select CF-related complications were less common in patients who
received KALYDECO. Patients who received KALYDECO from year one of
commercial availability had consistently better preserved lung function
and improved nutritional measures compared to matched untreated
patients. No new safety concerns were identified. These data further add
to the growing body of evidence showing disease modification by CFTR
modulator treatment.

In total, the analyses included 1,727 patients from the U.S. Cystic
Fibrosis Foundation Patient Registry (CFFPR) and 432 patients from the
U.K. Cystic Fibrosis Registry (CFR) who had received ivacaftor in 2015.

EVOLVE, EXPAND and EXTEND Phase 3 Studies of Tezacaftor/Ivacaftor

"Efficacy and Safety of Tezacaftor/Ivacaftor in Patients aged ≥12
with CF Homozygous for F508del-CFTR: A Randomized Placebo (PBO) -
Controlled Phase 3 Trial." Oral presentation S14.1 during Symposium
S14--NT: CF Interventions Advancing Through the Clinical Testing Phase.

"Efficacy and Safety of Tezacaftor/Ivacaftor in Patients aged ≥12
with CF Heterozygous for F508DEL and a Residual Function Mutation: A
randomized, double-blind, Placebo-Controlled, Crossover Phase 3 Study."
Oral presentation S14.2 during Symposium S14--NT: CF Interventions
Advancing Through the Clinical Testing Phase.

The first data from the ongoing 96-week EXTEND Phase 3 rollover study of
the tezacaftor/ivacaftor combination were presented during oral
presentations at NACFC. Patients who completed the Phase 3 EVOLVE and
EXPAND tezacaftor/ivacaftor studies were eligible to enter an open-label
Phase 3 rollover study, called EXTEND, to receive tezacaftor/ivacaftor
for 96 weeks. This preplanned interim analysis was conducted when
approximately 70 percent of patients from the EVOLVE study reached 24
weeks in the EXTEND study and when approximately 70 percent of patients
from the EXPAND study reached 16 weeks in the EXTEND study.

This analysis showed that the initial improvements in lung function
(measured by the absolute change in ppFEV1) observed in the
Phase 3 EVOLVE and EXPAND studies were sustained for up to 48 total
weeks of treatment (24 weeks in EVOLVE + 24 weeks in EXTEND, or 8 weeks
in EXPAND + 16 weeks in EXTEND). Safety data from this interim analysis
showed that tezacaftor/ivacaftor was generally well tolerated and had a
safety profile consistent with that seen in EVOLVE and EXPAND.

Triple Combination Regimens

"Preliminary Safety and Efficacy of Triple Combination CFTR Modulator
Regimens in CF." Poster 777. Oral presentation during Workshop W18--NT:
Innovative Approaches to CF Therapy.

Previously announced data from Phase
1 and Phase 2 studies
of three different next-generation correctors
(VX-440, VX-152 and VX-659) in combination regimens with tezacaftor and
ivacaftor were presented for the first time. These data demonstrate the
potential to treat the underlying cause of CF in people who have one F508del
mutation and one minimal function mutation not responsive to ivacaftor,
tezacaftor or the combination of tezacaftor/ivacaftor, a severe and
difficult-to-treat type of the disease. All studies showed statistically
significant improvements in lung function (ppFEV1) with a
triple combination regimen in these patients. In addition, initial data
from the studies of VX-440 and VX-152 showed improvements in lung
function with the addition of either next-generation corrector in people
with two copies of the F508del mutation who were already
receiving tezacaftor/ivacaftor. The triple combination regimens were
generally well tolerated across all three 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.

Data from additional ongoing Phase 2 studies are expected in early 2018.
Vertex plans to initiate pivotal development of up to two triple
combination regimens in the first half of 2018.

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 ORKAMBI® (lumacaftor/ivacaftor)

In people with two copies of the F508del mutation, the CFTR
protein is not processed and trafficked normally within the cell,
resulting in little-to-no CFTR protein at the cell surface. Patients
with two copies of the F508del mutation are easily
identified by a simple genetic test.

ORKAMBI is a combination of lumacaftor, which is designed to increase
the amount of mature protein at the cell surface by targeting the
processing and trafficking defect of the F508del-CFTR protein, and
ivacaftor, which is designed to enhance the function of the CFTR protein
once it reaches the cell surface. It is an oral pill taken every 12
hours - once in the morning and once in the evening.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR ORKAMBI® (lumacaftor/ivacaftor)
TABLETS

ORKAMBI is a prescription medicine used for the treatment of cystic
fibrosis (CF) in patients age 6 years and older who have two copies of
the F508del mutation (F508del/F508del) in their
CFTR gene. ORKAMBI should only be used in these patients. It is not
known if ORKAMBI is safe and effective in children under 6 years of age.

Patients should not take ORKAMBI if they are taking certain medicines
or herbal supplements, such as:
 the antibiotics rifampin or
rifabutin; the seizure medicines phenobarbital, carbamazepine, or
phenytoin; the sedatives/anti-anxiety medicines triazolam or midazolam;
the immunosuppressant medicines everolimus, sirolimus, or tacrolimus;
or St. John's wort.

Before taking ORKAMBI, patients should tell their doctor if they: have
or have had liver problems; have kidney problems; have had an organ
transplant; are using birth control (hormonal contraceptives, including
oral, injectable, transdermal or implantable forms). Hormonal
contraceptives should not be used as a method of birth control when
taking ORKAMBI. Patients should tell their doctor if they are pregnant
or plan to become pregnant (it is unknown if ORKAMBI will harm the
unborn baby) or if they are breastfeeding or planning to breastfeed (it
is unknown if ORKAMBI passes into breast milk).

ORKAMBI may affect the way other medicines work and other medicines may
affect how ORKAMBI works. Therefore, the dose of ORKAMBI or other
medicines may need to be adjusted when taken together. Patients should
especially tell their doctor if they take: antifungal medicines such as
ketoconazole, itraconazole, posaconazole, or voriconazole; or
antibiotics such as telithromycin, clarithromycin, or erythromycin.

When taking ORKAMBI, patients should tell their doctor if
they stop ORKAMBI for more than 1 week as the doctor may need to change
the dose of ORKAMBI or other medicines the patient is taking. It is
unknown if ORKAMBI causes dizziness. Patients should not drive a car,
use machinery, or do anything requiring alertness until the patient
knows how ORKAMBI affects them.

ORKAMBI can cause serious side effects including:

High liver enzymes in the blood, which can be a sign of liver injury,
have been reported in patients receiving ORKAMBI. 
The patient's
doctor will do blood tests to check their liver before they start
ORKAMBI, every three months during the first year of taking ORKAMBI, and
annually thereafter. The patient should call the 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; or confusion.

Respiratory events such as shortness of breath or chest tightness
were observed in patients when starting ORKAMBI. 
If a patient
has poor lung function, their doctor may monitor them more closely when
starting ORKAMBI.

An increase in blood pressure has been seen in some patients treated
with ORKAMBI. 
The patient's doctor should monitor their blood
pressure during treatment with ORKAMBI.

Abnormality of the eye lens (cataract) has been noted in some
children and adolescents receiving ORKAMBI and ivacaftor, a component of
ORKAMBI. 
For children and adolescents, the patient's doctor
should perform eye examinations prior to and during treatment with
ORKAMBI to look for cataracts.

The most common side effects of ORKAMBI include: shortness of breath
and/or chest tightness; upper respiratory tract infection (common cold),
including sore throat, stuffy or runny nose; gastrointestinal symptoms
including nausea, diarrhea, or gas; rash; fatigue; flu or flu-like
symptoms; increase in muscle enzyme levels; and irregular, missed, or
abnormal menstrual periods and heavier bleeding.

Please click here to
see the full Prescribing Information for ORKAMBI.

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, statements in the second and sixth paragraphs and statements
regarding the timing of and development plan with respect to the
next-generation triple combination regimens. 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, that Vertex could experience
unforeseen delays in conducting its development programs 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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