Vertex Submits Supplemental New Drug Application (sNDA) to U.S. Food and Drug Administration for KALYDECO™ (ivacaftor)

  Vertex Submits Supplemental New Drug Application (sNDA) to U.S. Food and
  Drug Administration for KALYDECO™ (ivacaftor) Monotherapy for People with
  Non-G551D Gating Mutations

   -sNDA also includes long-term safety and efficacy data for KALYDECO from
                      PERSIST open-label rollover study-

  -Marketing Authorization Application (MAA) variation inEurope planned for
                                October 2013-

Business Wire

CAMBRIDGE, Mass. -- September 30, 2013

Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) today announced the
submission of a supplemental New Drug Application (sNDA) to the U.S. Food and
Drug Administration (FDA) for the approval of KALYDECO^TM (ivacaftor)
monotherapy for people with cystic fibrosis (CF) ages 6 and older who have at
least one non-G551D gating mutation in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene. KALYDECO is currently approved for people
with CF ages 6 and older who have at least one copy of the G551D mutation. CF
is caused by a defective CFTR protein that results from mutations in the CFTR
gene. G551D is known as a gating mutation, and there are an additional nine
known gating mutations. Gating mutations prevent the CFTR protein from opening
or working (gating) properly at the cell surface. Worldwide, approximately
2,000 people with CF ages 6 and older have at least one copy of the G551D
mutation, and approximately 400 people with CF ages 6 and older have at least
one non-G551D gating mutation.

"Today’s submission to the FDA is an important step toward our goal of helping
more people with CF," saidRobert Kauffman, M.D., Ph.D., Senior Vice President
and Chief Medical Officer at Vertex. “The study in people with non-G551D
gating mutations is the first of multiple ongoing efforts to expand the number
of people who may benefit from ivacaftor, and we expect additional data from
these ongoing studies beginning later this year.”

The sNDA submission is based on previously announced data from a Phase 3study
of ivacaftor monotherapy that showed statistically significant improvements in
lung function (FEV[1]). The mean absolute treatment difference in percent
predicted FEV[1]between treatment with ivacaftor and placebo was 10.7% (p <
0.0001) and the mean relative treatment difference in percent predicted
FEV[1]was 14.2% (p < 0.0001) through the 8-week treatment period. The safety
and tolerability results observed in this study were consistent with those
observed in prior Phase 3 studies of ivacaftor monotherapy in people with CF
who have the G551D mutation. The study in gating mutations is one of three
ongoing Phase 3 label-expansion studies designed to evaluate whether
additional people with CF may benefit from treatment with ivacaftor alone.

In addition to the sNDA submission, Vertex intends to submit a Marketing
Authorization Application (MAA) variation inEuropein October 2013 for people
with CF ages 6 and older who have at least one non-G551D gating mutation.

As part of the sNDA package, Vertex also submitted long-term data from the
96-week PERSIST open-label study of KALYDECO. PERSIST is an ongoing rollover
study of people with cystic fibrosisages 6 and older with a G551D mutation
who took part in the 48-week Phase 3 STRIVE and ENVISON studies of KALYDECO.
The data from PERSIST submitted as part of the sNDA included efficacy and
safety results through 144 weeks of continuous treatment with KALYDECO.

The non-G551D gating data and the long-term PERSIST data will be presented at
the 27thAnnualNorth American Cystic Fibrosis Conference(NACFC) inSalt Lake
City, Utah,October 17-19, 2013. Vertex expects the gating data to be
presented as an oral presentation during Symposium III, "CFTR: Matching CFTR
Mutations and Drugs," onOctober 19.


KALYDECO™ (ivacaftor) is the first medicine to treat the underlying cause of
CF in people with the G551D mutation 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, 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.


Ivacaftor (150mg 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

Ivacaftor is not for use in people with CF due to other mutations in
theCFTRgene. It is not effective in patients with CF with 2 copies of the
F508del mutation (F508del/F508del) in theCFTRgene. The efficacy and safety
of ivacaftor in children younger than 6 years of age have not been evaluated.

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 which may diminish
effectiveness. Therefore, co-administration is not recommended.

The dose of ivacaftor must be adjusted when used concomitantly with potent and
moderate CYP3A inhibitors. The dose of ivacaftor must be adjusted 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 full U.S. Prescribing Information for KALYDECO,
the EU Summary of Product Characteristics for KALYDECO at,
the Canadian Product Monograph for KALYDECO at and the Australian
Consumer Medical Information and Product Information for KALYDECO

About Cystic Fibrosis

Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 70,000 people worldwide, including 30,000 people in the United
States, 35,000 in Europe, 4,000 in Canada and 3,000 in 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 1,800 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 absence of working CFTR protein 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.

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 creates new possibilities in medicine. Our team discovers, develops and
commercializes innovative therapies 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 hepatitis C, cystic fibrosis,
rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing
worldwide research programs and sites in the U.S., U.K. and Canada. Today,
Vertex has more than 2,000 employees around the world, and for three years in
a row, Science magazine has named Vertex one of its Top Employers in the life

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 second paragraph of this press
release and statements regarding (i) Vertex’s plan to submit a Marketing
Authorization Application (MAA) variation in Europe and (ii) the data that
will be presented at the NACFC conference. While the company 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 Vertex could
experience unforeseen delays in obtaining approval to market ivacaftor for
people with non-G551D gating mutations and the other risks listed under Risk
Factors in Vertex's annual report and quarterly reports filed with the
Securities and Exchange Commission and available through Vertex's website at Vertex disclaims any obligation to update the information
contained in this press release as new information becomes available.



Vertex Pharmaceuticals Incorporated
Michael Partridge, 617-341-6108
Kelly Lewis, 617-961-7530
North America: Zach Barber, 617-341-6470
Europe: Megan Goulart, +41 22 593 6066
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