Vertex Data Presented at North American Cystic Fibrosis Conference (NACFC) Demonstrate Rapid Progress Toward Expanding and Enhancing Options for Treating the Underlying Cause of Cystic Fibrosis

– 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) –

DENVER–(BUSINESS WIRE)–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)

Contacts

Vertex Pharmaceuticals Incorporated
Investors:
Michael
Partridge, 617-341-6108
or
Eric Rojas, 617-961-7205
or
Zach
Barber, 617-341-6470
or
Media:
North America:
Heather
Nichols, 617-341-6992
mediainfo@vrtx.com
or
Europe
& Australia:
Rebecca Hunt, +44 7718 962 690

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