U.S. Food and Drug Administration Approves KALYDECO™ (ivacaftor) for Use in Eight Additional Mutations that Cause Cystic

  U.S. Food and Drug Administration Approves KALYDECO™ (ivacaftor) for Use in
  Eight Additional Mutations that Cause Cystic Fibrosis

-KALYDECO is the first medicine to treat the underlying cause of CF for people
                  with specific mutations in the CFTR gene-

    -KALYDECO facilitates increased chloride transport by potentiating the
          channel-open probability (or gating) of the CFTR protein-

 -The eight additional mutations are present in approximately 150 people ages
                     six and older in the United States-

Business Wire

BOSTON -- February 21, 2014

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the U.S.
Food and Drug Administration (FDA) approved a supplemental New Drug
Application (sNDA) for KALYDECO^TM (ivacaftor) for people with cystic fibrosis
(CF) ages 6 and older who have one of eight additional mutations in the cystic
fibrosis transmembrane conductance regulator (CFTR) gene. KALYDECO was first
approved in January 2012 for people with CF ages 6 and older who have at least
one copy of the G551D mutation. With the approval of the sNDA, KALYDECO is now
approved for use in people with CF with the following nine mutations: G551D,
G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In the United
States, approximately 150 people ages 6 and older have one of the additional
eight mutations for which KALYDECO is now approved.

CF is caused by defective or missing CFTR proteins that result from mutations
in the CFTR gene. The defective function or absence of CFTR proteins in people
with CF results in poor flow of salt and water into and out of the cell in a
number of organs, including the lungs. Ivacaftor facilitates increased
chloride transport by potentiating the channel-open probability (or gating) of
the CFTR protein.

“We believe that KALYDECO has the potential to help more people with CF, and
today’s approval is an important step toward that goal," saidRobert Kauffman,
M.D. Ph.D., Senior Vice President and Co-Chief Medical Officer at Vertex. “As
we progress over the coming year, we look forward to data from multiple other
ongoing studies that are designed to evaluate whether additional people with
CF may benefit from KALYDECO.”

KALYDECO was granted Breakthrough Therapy designation by the U.S. FDA in late
2012. The sNDA approval is based on previously announced data from a Phase 3,
two-part, randomized, double-blind, placebo-controlled, cross-over study of 39
people with CF who had one of the following mutations: G178R, S549N, S549R,
G551S, G1244E, S1251N, S1255P, G1349D or G970R. The study showed statistically
significant improvements in lung function (FEV[1]) for people in the overall
study population who received ivacaftor, and the safety profile was similar to
prior Phase 3 studies in people with the G551D mutation. Based on data from
four patients with the G970R mutation enrolled in the study, the efficacy of
KALYDECO in patients with the G970R mutation could not be established to
support approval in the U.S. Vertex estimates that approximately 10 people
with CF have the G970R mutation worldwide, including two people in the United
States.

Data from the study noted above were also used to support regulatory
submissions in Europe, Canada and Australia for approval of KALYDECO in
additional people with CF ages 6 and older. In Europe and Australia,
approximately 250 people with CF have these additional mutations.

Vertex today reaffirmed its 2014 net revenue guidance for KALYDECO as provided
on January 29, 2014.

About KALYDECO^TM (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 that aims to help the CFTR protein
function more normally once it reaches the cell surface, to help hydrate and
clear mucus from the airways. KALYDECO (150mg, q12h) was first approved by the
U.S. Food and Drug Administration in January 2012 for use in people with CF
ages 6 and older who have at least one copy of the G551D mutation and in
February 2014 for use in people with CF ages 6 and older who have the
following additional CFTR mutations: G178R, S549N, S549R, G551S, G1244E,
S1251N, S1255P and G1349D.

KALYDECO was approved by the European Medicines Agency in July 2012, by Health
Canada in November 2012 and by the Therapeutic Goods Administration in
Australia in July 2013 for use in people with CF ages 6 and older who have at
least one copy of the G551D mutation in the CFTR gene.

Vertex retains worldwide rights to develop and commercialize KALYDECO.

About Cystic Fibrosis

Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 75,000 people in North America, Europe and Australia. Today, the
median predicted age of survival for a person with CF is between 34 and 47
years, but the median age of death remains in the mid-20s.

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 more than 1,900 known mutations in the
CFTR gene. Some of these mutations, which can be determined by a genetic, or
genotyping test, lead to CF by creating non-working or too few CFTR protein at
the cell surface. The defective function or absence of CFTR proteins in people
with CF results in poor flow of salt and water into and 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.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc.
(CFFT)

Vertex initiated its CF research program in 1998 as part of a collaboration
with CFFT, the nonprofit drug discovery and development affiliate of the
Cystic Fibrosis Foundation. This collaboration was expanded to support the
accelerated discovery and development of Vertex's CFTR modulators.

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. Vertex scientists and our collaborators are working on new
medicines to cure or significantly advance the treatment of cystic fibrosis,
hepatitis C, rheumatoid arthritis and other life-threatening diseases. In
addition to our clinical development programs, Vertex has more than a dozen
ongoing preclinical 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 four 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.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO™ (ivacaftor)

Ivacaftor (150 mg tablets) is indicated for the treatment of cystic fibrosis
(CF) in patients age 6 years and older who have a G551D mutation in the CFTR
gene.

In the United States only, ivacaftor is also indicated for the treatment of CF
in patients age 6 and older who have one of the following mutations in the
CFTR gene: G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

Ivacaftor is not effective in patients with CF with 2 copies of the F508del
mutation (F508del/F508del) in theCFTRgene. The safety and efficacy of
ivacaftor in children with CF younger than 6 years of age have not been
established.

Elevated liver enzymes (transaminases; ALT and AST) have been reported in
patients receiving ivacaftor. It is recommended that ALT and AST be assessed
prior to initiating ivacaftor, every 3 months during the first year of
treatment, and annually thereafter. Patients who develop increased
transaminase levels should be closely monitored until the abnormalities
resolve. Dosing should be interrupted in patients with ALT or AST of greater
than 5 times the upper limit of normal. Following resolution of transaminase
elevations, consider the benefits and risks of resuming ivacaftor dosing.

Use of ivacaftor with medicines that are strong CYP3A inducers, such as the
antibiotics rifampin and rifabutin; seizure medications (phenobarbital,
carbamazepine, or phenytoin); and the herbal supplement St. John's Wort,
substantially decreases exposure of ivacaftor and may diminish effectiveness.
Therefore, co-administration is not recommended.

The dose of ivacaftor must be adjusted when used concomitantly with strong and
moderate CYP3A inhibitors or when used in patients with moderate or severe
hepatic disease.

Ivacaftor can cause serious adverse reactions including abdominal pain and
high liver enzymes in the blood. The most common side effects associated with
ivacaftor include headache; upper respiratory tract infection (the common
cold), including sore throat, nasal or sinus congestion, and runny nose;
stomach (abdominal) pain; diarrhea; rash; and dizziness. These are not all the
possible side effects of ivacaftor. A list of the adverse reactions can be
found in the product labeling for each country where ivacaftor is approved.
Patients should tell their healthcare providers about any side effect that
bothers them or does not go away.

Please see KALYDECO U.S. Prescribing Information, EU Summary of Product
Characteristics, Canadian Product Monograph, Australian Consumer Medicine
Information and Product Information, Swiss Prescribing Information and Patient
Information, and the New Zealand Datasheet and Consumer Medicine Information.

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, Dr. Kauffman's statements in the third paragraph of the press
release and statements regarding Vertex’s expectations regarding 2014 KALYDECO
net revenues. 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 its 2014 KALYDECO net revenues may be incorrect
(including because one or more of the company's assumptions underlying its
revenue 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
theSecurities and Exchange Commissionand available through the company's
website atwww.vrtx.com. Vertex disclaims any obligation to update the
information contained in this press release as new information becomes
available.

(VRTX-GEN)

Contact:

Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, 617-341-6108
or
Kelly Lewis, 617-961-7530
or
Media:
Zach Barber, 617-341-6992
mediainfo@vrtx.com
 
Press spacebar to pause and continue. Press esc to stop.