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Phase 3 Studies of the Tezacaftor/Ivacaftor Combination Treatment in People with Cystic Fibrosis Ages 12 and Older Published in the New England Journal of Medicine

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- Data showed significant improvements in lung function (ppFEV1)
with a favorable safety profile across multiple patient groups -

- Tezacaftor/ivacaftor currently under review by the FDA and EMA; FDA
Priority Review action date of February 28, 2018 -

Vertex
Pharmaceuticals Incorporated
(NASDAQ:VRTX) announced today that the New
England Journal of Medicine
(NEJM) published two articles
with results from two
Phase 3 studies
of the tezacaftor/ivacaftor combination treatment, a
medicine in development that is designed to treat the underlying cause
of cystic fibrosis (CF) in people ages 12 and older who have certain
mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
gene. In both studies, the tezacaftor/ivacaftor combination demonstrated
statistically significant and clinically meaningful improvements in lung
function and other measures of disease. The EVOLVE
study
evaluated the combination in people who have two copies of the F508del
mutation, the most common mutation in the CFTR gene. The EXPAND
study
evaluated the combination in people with one F508del
mutation and one mutation that results in residual CFTR function. The
results were published in two online articles today in conjunction with
two oral presentations at the 31st Annual North American Cystic Fibrosis
Conference, November 2 to 4, 2017 in Indianapolis. These data formed the
basis of applications for the approval of the tezacaftor/ivacaftor
combination that are currently under review with regulatory agencies in
the United States and Europe. In the United States, the Food and Drug
Administration (FDA) has granted Priority Review of the application and
has set an action date of February 28, 2018.

"We have made unprecedented progress in the treatment of CF in recent
years, but we continue to drive ourselves to deliver even greater
benefits for patients today and more new medicines for patients who are
still waiting," said Jeffrey Chodakewitz, M.D., Executive Vice President
and Chief Medical Officer at Vertex. "These tezacaftor/ivacaftor results
are exciting because they represent the potential to do both."

Summary of Key Data from EVOLVE

The 24-week EVOLVE study evaluated tezacaftor/ivacaftor in more than 500
people with CF ages 12 and older who have two copies of the F508del mutation.
Improvements across multiple disease measures, including lung function,
were demonstrated among patients treated with tezacaftor/ivacaftor
compared to those who received placebo. There was also a reduction in
pulmonary exacerbations among those treated with tezacaftor/ivacaftor.

"In this study, the tezacaftor/ivacaftor combination demonstrated
significant, clinically meaningful improvements in lung function and
other measures of cystic fibrosis health status," said Jennifer
Taylor-Cousar, M.D., co-lead author of the EVOLVE study 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. "Tezacaftor/ivacaftor was also very
well tolerated, which makes it an important potential new option for
helping our patients feel better and change the course of their disease.
The fact that tezacaftor/ivacaftor will be the basis of triple
combination therapy makes this positive data even more exciting for
patients with CF and the physicians who care for them."

Lung Function: Progressive lung disease is a major source of
illness and is the leading cause of death in people with CF. The study
met its primary endpoint with a mean absolute improvement in lung
function (measured as percent predicted forced expiratory volume in one
second, or ppFEV1) through 24 weeks of 4.0 percentage points
from baseline compared to placebo (p<0.0001). This equates to a mean
relative improvement (a key second endpoint in the study), which is an
assessment of the percentage change, of 6.8 percent (p<0.0001).

Pulmonary Exacerbations: Pulmonary exacerbations are episodes of
worsening signs and symptoms of the disease that often require treatment
with intravenous antibiotics or hospitalization. Through the 24-week
study, those receiving tezacaftor/ivacaftor had a 35 percent reduction
in the annualized rate of pulmonary exacerbations compared to those on
placebo (p=0.0054). In addition, patients receiving tezacaftor/ivacaftor
were 47 percent less likely to experience a pulmonary exacerbation that
required hospitalization or intravenous antibiotics than those receiving
placebo (p=0.0042).

Body Mass Index: Body mass index, or BMI, is a measure of body
fat based on a person's height and weight. For people with CF, BMI is
one way of assessing nutritional status; poor nutritional status, and
thus lower BMI, is associated with worse lung function. In EVOLVE,
people receiving tezacaftor/ivacaftor had a non-statistically
significant BMI increase of 0.06 compared to those receiving placebo
(p=0.4127).

Patient-Reported Outcomes: The Cystic Fibrosis Questionnaire —
Revised (CFQ-R) is a validated patient-reported outcome tool that was
used in the EVOLVE study to measure the impact of tezacaftor/ivacaftor
on overall health, daily life, perceived well-being and symptoms. One
aspect of the CFQ-R, referred to as the respiratory domain, addresses
patient reported symptoms including things such as coughing, congestion,
wheezing and other respiratory symptoms. In EVOLVE, the mean absolute
improvement in the respiratory domain of CFQ-R at Week 24 was 5.1
compared to those receiving placebo (p<0.0001). This increase is
considered nominally statistically significant.

Safety: The tezacaftor/ivacaftor combination treatment was
generally well tolerated. The majority of adverse events were mild or
moderate. The most common adverse events (≥15%), regardless of treatment
group, were infective pulmonary exacerbation, cough, headache,
nasopharyngitis and sputum increased. The rate of discontinuations due
to adverse events was low and similar between the placebo group and the
combination treatment group. Rates of adverse events, serious adverse
events and respiratory-related adverse events were similar between the
placebo and the tezacaftor/ivacaftor combination treatment groups.

Summary of Key Data from EXPAND

The EXPAND study evaluated eight weeks of treatment with the
tezacaftor/ivacaftor combination, ivacaftor monotherapy or placebo in
approximately 250 people with CF ages 12 and older who have one F508del
mutation and one mutation that results in residual CFTR function.
Improvements across multiple disease measures, including lung function,
were demonstrated among patients treated with tezacaftor/ivacaftor and
those treated with ivacaftor alone in the study compared to those who
received placebo.

"This is an exciting time to be part of cystic fibrosis research as we
continue to improve outcomes for patients," said Steven M. Rowe, M.D.,
M.S.P.H., co-lead author of the EXPAND study and Professor of Medicine,
Pediatrics, and Cell, Developmental and Integrative Biology, Director of
the Gregory Fleming James Cystic Fibrosis Research Center, Nancy and
Eugene Gwaltney Endowed Chair in Medical Research, University of Alabama
at Birmingham. "These results are particularly exciting because they
demonstrate that by addressing the underlying cause of cystic fibrosis,
the tezacaftor/ivacaftor combination offers significant benefits for
many people with this severe and life-shortening disease, while also
offering increased benefit over KALYDECO alone in patients with residual
function mutations."

Lung Function: The EXPAND study met its primary endpoint of
absolute improvement in lung function, with those receiving
tezacaftor/ivacaftor demonstrating a mean absolute improvement of 6.8
percentage points compared to placebo (p<0.0001) and the ivacaftor
monotherapy group demonstrating a mean absolute improvement of 4.7
percentage points compared to placebo (p<0.0001). Improvements in lung
function were measured as the change in ppFEV1 from the start
of the study (baseline) to the average of the Week 4 and Week 8
measurements. An additional pre-specified analysis showed that the
tezacaftor/ivacaftor combination treatment provided a statistically
significant improvement in ppFEV1 over ivacaftor alone (2.1
percentage points, p<0.0001).

Patient-Reported Outcomes: In EXPAND, the mean absolute
improvement in the respiratory domain of CFQ-R (the key secondary
endpoint), measured as the average of the Week 4 and Week 8
measurements, was 11.1 for those receiving tezacaftor/ivacaftor and was
9.7 for those receiving ivacaftor, both compared to placebo (p<0.0001).

Safety: In the EXPAND study, the safety profile observed for the
tezacaftor/ivacaftor combination treatment was favorable and similar to
that seen in the EVOLVE study. Tezacaftor/ivacaftor combination
treatment and ivacaftor monotherapy were both generally well tolerated.
The majority of adverse events were mild or moderate. The most common
adverse events (≥15%), regardless of treatment group, were cough and
infective pulmonary exacerbation. There were no discontinuations due to
adverse events in the combination treatment group. Discontinuations due
to adverse events were low and similar between the placebo group and the
ivacaftor monotherapy group. The incidence of adverse events, serious
adverse events and respiratory-related adverse events was similar
between the placebo, tezacaftor/ivacaftor combination and ivacaftor
monotherapy groups.

About Cystic Fibrosis

Cystic Fibrosis (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 cystic fibrosis transmembrane
conductance regulator (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.

In people with the F508del mutation, the CFTR protein is not
processed, or folded, normally within the cell and generally does not
reach the cell surface. Tezacaftor is designed to address the processing
defect of F508del-CFTR to enable it to reach the cell surface
where ivacaftor can further enhance the protein's function.

In North America, Europe and Australia, there are more than 22,000
people ages 12 and older who have two copies of the F508del
mutation, and there are more than 1,500 people ages 12 and older who
have at least one residual function mutation that is responsive to
tezacaftor/ivacaftor in vitro or in the clinic.

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, fourth and eleventh paragraphs and
statements regarding the tezacaftor/ivacaftor combination and the timing
of the potential regulatory approval of the tezacaftor/ivacaftor
combination. 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, (i) that regulatory
authorities may not approve, or approve on a timely basis, the
tezacaftor/ivacaftor combination due to safety, efficacy or other
reasons, and (ii) 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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