Market Overview

FDA Approves KALYDECO® (ivacaftor) as First and Only Medicine to Treat the Underlying Cause of CF in Children Ages 12 to <24 Months with Certain Mutations in the CFTR Gene

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-Data from Phase 3 ARRIVAL study support treatment with KALYDECO in
children ages 12 to <24 months-

Vertex
Pharmaceuticals Incorporated
(NASDAQ:VRTX) today announced the U.S.
Food and Drug Administration (FDA) approved KALYDECO® (ivacaftor)
to include use in children with cystic fibrosis (CF) ages 12 to <24
months who have at least one mutation in their cystic fibrosis
transmembrane conductance regulator (CFTR) gene that is
responsive to KALYDECO based on clinical and/or in vitro assay
data.

"Cystic fibrosis is a chronic, progressive disease that is present at
birth, with symptoms often occurring in infancy," said Reshma
Kewalramani, M.D., Executive Vice President and Chief Medical Officer at
Vertex. "With today's approval, parents and physicians now have a
medicine to treat the underlying cause of CF in patients as young as one
year of age. We are excited about the progress of our portfolio and
continue to support additional research on the potential benefit of
early intervention with all of our medicines, with the goal of bringing
a treatment to all people living with CF."

This FDA approval is based on data from the ongoing Phase 3 open-label
safety study (ARRIVAL) of 25 children with CF aged 12 to <24 months who
have one of 10 mutations in the CFTR gene (G551D, G178R,
S549N, S549R, G551S, G1244E, S1251N, S1255P,
G1349D or R117H). The study demonstrated a safety profile
consistent with that observed in previous Phase 3 studies of older
children and adults; most adverse events were mild or moderate in
severity, and no patient discontinued due to adverse events. Two
patients had elevated liver enzymes greater than eight times the upper
limit of normal, but continued to receive KALYDECO after a dose
interruption. The most common adverse events (≥30%) were cough (74%),
pyrexia (37%), elevated aspartate aminotransferase (37%), elevated
alanine aminotransferase (32%) and runny nose (32%). Four serious
adverse events were observed in two patients.

Mean baseline sweat chloride for the children in this study was 104.1
mmol/L (n=14). Following 24 weeks of treatment with KALYDECO, the mean
sweat chloride level was 33.8 mmol/L (n=14). In the 10 subjects with
paired sweat chloride samples at baseline and week 24, there was a mean
absolute change of -73.5 mmol/L. These data were presented at the 41st
European Cystic Fibrosis Society (ECFS) Conference in June 2018 and
published in The Lancet Respiratory Medicine (Volume 6, No 7,
July 2018).

"I'm very excited about the approval of ivacaftor in children ages 12 to
less than 24 months as this is the first regulatory approval of a CFTR
modulator in this age group," said Margaret Rosenfeld, M.D., MPH,
Seattle Children's Research Institute and Department of Pediatrics,
University of Washington School of Medicine. "The premise of newborn
screening for CF is to intervene very early in the course of disease
with the goal of improving long term outcomes, so this is a significant
milestone for parents and caregivers of young children with CF."

KALYDECO was already approved in the U.S. for the treatment of CF in
patients ages 2 and older who have one of 38 ivacaftor-responsive
mutations in the CFTR gene based on clinical and/or in vitro
assay data. Vertex submitted a Marketing Authorization Application for a
line extension (ages 12 to <24 months) to the European Medicines Agency
with a decision anticipated in the first half of 2019.

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.

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 ages 12 months 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.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO® (ivacaftor)
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 take 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.

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), SYMDEKO®
(tezacaftor/ivacaftor and ivacaftor), 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 second and fifth paragraphs of the
press release and statements regarding the Marketing Authorization
Application for a line extension submitted to the European Medicines
Agency. 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 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)

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