U.S. Food and Drug Administration Approves ORKAMBI® (lumacaftor/ivacaftor) for Use in Children with Cystic Fibrosis Ages 6 through 11 who have Two Copies of the F508del Mutation

-Approximately 2,400 children ages 6 through 11 have two copies of
the F508del mutation in the U.S.-

– Vertex revises ORKAMBI revenue guidance for 2016 –

BOSTON–(BUSINESS WIRE)–Vertex
Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced that the
U.S. Food and Drug Administration (FDA) approved ORKAMBI®
(lumacaftor/ivacaftor) for use in children with cystic fibrosis (CF)
ages 6 through 11 who have two copies of the F508del mutation.
People with this mutation represent the largest population of those with
CF, a rare, life-threatening disease. ORKAMBI is the first and only
medicine to treat the underlying cause of CF for people with this
mutation. It was previously approved by the FDA for use in people ages
12 and older with two copies of the F508del mutation. With
today’s approval, approximately 11,000 people with CF are eligible for
treatment with ORKAMBI in the United States. ORKAMBI will be available
for eligible children ages 6 through 11 in the United States as soon as
possible. Vertex also today lowered its guidance for 2016 ORKAMBI
revenues to a range of $950 million to $990 million.

“The ability to treat children as young as six who have the most common
form of the disease is an important milestone as we pursue our goal to
develop medicines for all people with CF,” said Jeffrey Chodakewitz,
M.D., Executive Vice President and Chief Medical Officer at Vertex. “We
believe it is important to treat the underlying cause of the disease as
early as possible in these patients.”

The approval is based on data from a previously announced open-label
Phase 3 clinical safety study of ORKAMBI presented at the 39th
European Cystic Fibrosis Society Conference in June 2016. These data
will be presented at the 30th Annual North American Cystic
Fibrosis Conference October 27-29 in Orlando, Florida.

Vertex plans to submit a Marketing Authorization Application (MAA)
variation in the European Union in the first half of 2017 for children
ages 6 through 11 who have two copies of the F508del mutation. This
application will be based on data from a Phase 3 efficacy study with a
primary endpoint of absolute change in lung clearance index (LCI). These
data are expected before the end of 2016.

ORKAMBI Financial Guidance

Vertex today revised its guidance for 2016 ORKAMBI revenues. The company
now expects ORKAMBI revenues of $950 million to $990 million. Vertex’s
prior guidance was for total 2016 ORKAMBI revenues of $1.0 billion to
$1.1 billion, and to date Vertex has reported ORKAMBI revenues of $223
million and $245 million for the first and second quarters of 2016,
respectively. Vertex expects third quarter ORKAMBI revenues to be
between $230 million and $235 million. The revised guidance primarily
reflects the following:

  • The slower than anticipated launch in Germany where fewer than 20
    percent of the approximately 2,500 eligible patients have initiated
    treatment to date;
  • That we are approaching peak penetration for ORKAMBI in the U.S. where
    there are approximately 8,500 eligible patients ages 12 and older; and
  • Slower than expected refills for ORKAMBI during the summer months of
    July and August.

Today’s approval in people ages 6 through 11 will drive growth in the
U.S. in the fourth quarter of 2016. Growth for ORKAMBI in 2017 will be
driven both by obtaining reimbursement approvals in key European and
other countries and by continued growth among eligible patients ages 6
through 11 in the U.S.

About Cystic Fibrosis and ORKAMBI

Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 75,000 people in North America, Europe and Australia.

CF is caused by defective or missing cystic fibrosis conductance
regulator (CFTR) proteins 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, lead to CF by creating
defective or too few CFTR proteins at the cell surface. The defective or
missing CFTR protein results in poor flow of salt and water into or out
of the cell in a number of organs, including 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 predicted age of survival for a
person born today with CF in the United States is 39 years, but the
median age of death is 29 years.

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. In pediatric patients ages 6
through 11, two ORKAMBI tablets (each containing lumacaftor
100mg/ivacaftor 125mg) are taken orally every 12 hours – once in the
morning and once in the evening – with fat-containing food.

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.

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. ORKAMBI
(lumacaftor/ivacaftor) was discovered by Vertex as part of this
collaboration.

About Vertex

Vertex is a global biotechnology company that aims to discover, develop
and commercialize innovative medicines so people with serious diseases
can lead better lives. In addition to our clinical development programs
focused on cystic fibrosis, Vertex has more than a dozen ongoing
research programs aimed at other serious and life-threatening diseases.

Founded in 1989 in Cambridge, Mass., Vertex today has research and
development sites and commercial offices in the United
States, Europe, Canada and Australia. For six years in a row, Science magazine
has named Vertex one of its Top Employers in the life sciences. For
additional information and the latest updates from the company, please
visit www.vrtx.com.

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 information provided in Dr. Chodakewitz’s quote in the
second paragraph of this press release and in the section captioned
“ORKAMBI Financial Guidance” and statements regarding (i) Vertex’s
revenue guidance and expectations and (ii) plans to submit an MAA
variation in the European Union for children ages 6 to 11 who have two
copies of the F508del mutation and the timing of expected data from
Vertex’s Phase 3 efficacy study in this patient population. 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 the
company’s expectations regarding revenues may be incorrect (including
because one or more of the company’s assumptions underlying its
expectations may not be realized), 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:
Chris
Stamm, +1 617-341-6992
mediainfo@vrtx.com
or
Europe
& Australia:
Megan Goulart, +44 20 3204 5275
mediainfo@vrtx.com

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