FDA Approves KALYDECO® (ivacaftor) as First and Only CFTR Modulator to Treat Eligible Infants with CF as Early as Six Months of Age

-Opportunity to treat the underlying cause of CF earlier than ever
before-

-Safety data from Phase 3 ARRIVAL study support treatment with
KALYDECO in children ages six to <12 months with eligible mutations-

BOSTON–(BUSINESS WIRE)–lt;a href=”https://twitter.com/hashtag/cf?src=hash” target=”_blank”gt;#cflt;/agt;–Vertex
Pharmaceuticals Incorporated (Nasdaq:VRTX) today announced the U.S.
Food and Drug Administration (FDA) approved KALYDECO^® (ivacaftor)
for use in children with cystic fibrosis (CF) ages six months to less
than 12 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. KALYDECO is already approved in the U.S., Canada and EU for the
treatment of CF in patients ages 12 months and older.

“Today’s approval for KALYDECO allows physicians to begin treating the
underlying cause of CF in eligible infants as young as six months of age
for the first time, with the potential to modify the course of the
disease,” said Margaret Rosenfeld, M.D., MPH, Seattle Children’s
Research Institute and Department of Pediatrics, University of
Washington School of Medicine.

This FDA approval is based on data from a 24-week Phase 3 open-label
safety cohort (ARRIVAL) of 11 children with CF aged six months to less
than 12 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 similar to 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 therapy due to adverse events. The
most common adverse events (≥30%) were cough (64%), nasal congestion
(36%) and rhinorrhea (36%). Three serious adverse events, all considered
unrelated to study treatment by the investigators, were observed in
three patients.

Mean baseline sweat chloride for the children in this cohort was 101.5
mmol/L (n=11). Following 24 weeks of treatment with KALYDECO, the mean
sweat chloride level was 43.1 mmol/L (n=6). In the six subjects with
paired sweat chloride samples at baseline and week 24, there was a mean
absolute change of -58.6 mmol/L (95% CI; -75.9, -41.3).

Results of this study were presented at the 32nd Annual North American
Cystic Fibrosis Conference in October 2018.

“The manifestations of CF are often present at birth, which underscores
our relentless commitment to reach the youngest CF patients possible in
our clinical trials,” said Reshma Kewalramani, M.D., Executive Vice
President and Chief Medical Officer at Vertex. “As an important outcome
of these efforts, we are now able to treat infants with cystic fibrosis
as early as six months of age with KALYDECO.”

KALYDECO was first approved in 2012 in the U.S. and is now available in
more than 40 countries with more than 5,000 patients on therapy. For
more information on KALYDECO, prescribing information, or patient
assistance programs, visit Kalydeco.com
or VertexGPS.com.

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. It is also available as 25 mg, 50 mg and
75 mg granules in pediatric patients ages 6 months to less than 6 years.

People with CF who have specific mutations in the CFTR gene are
currently indicated for KALYDECO in different countries across North
America, Europe and other International markets.

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 6 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 6 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, 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 nine 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 sixth paragraphs of the press release.
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)

Contacts

Vertex Pharmaceuticals Incorporated
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Partridge, 617-341-6108
or
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or
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or
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