Republic of Ireland Approves Funding for KALYDECO™ (ivacaftor), the First Medicine to Treat the Underlying Cause of Cystic

  Republic of Ireland Approves Funding for KALYDECO™ (ivacaftor), the First
  Medicine to Treat the Underlying Cause of Cystic Fibrosis, for People with a
  Specific Genetic Mutation (G551D)

Business Wire

CAMBRIDGE, Mass. -- February 1, 2013

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that the
Health Service Executive (HSE) in the Republic of Ireland will fund KALYDECO™
(ivacaftor), the first medicine to treat the underlying cause of cystic
fibrosis (CF), for people ages 6 and older who have at least one copy of the
G551D mutation in the cystic fibrosis transmembrane conductance regulator
(CFTR) gene. Cystic fibrosis is a rare genetic disease for which there is no
cure. It is caused by a defective or missing CFTR protein resulting from
mutations in the CFTR gene. In people with the G551D mutation, ivacaftor helps
the defective CFTR protein function more normally.

Today’s decision follows an assessment of the medicine by the National Centre
for Pharmacoecomomics (NCPE), which acknowledged the benefits of ivacaftor,
including significant improvement in lung function, increased body weight,
improvement in quality of life and a 55 percent reduction in pulmonary
exacerbations, or periods of worsening respiratory signs and symptoms that
often require treatment with antibiotics and hospitalisation. Vertex is
working to make ivacaftor available to eligible people in Ireland as quickly
as possible.

“We are delighted that the HSE will make ivacaftor available for eligible
people with cystic fibrosis in Ireland,” said Simon Bedson, General Manager of
Vertex Europe. “We will work with them to help implement this decision to
ensure that those who are eligible can access ivacaftor as quickly as

Ivacaftor was discovered as part of a collaboration with Cystic Fibrosis
Foundation Therapeutics, Inc., the non-profit drug discovery and development
affiliate of the Cystic Fibrosis Foundation.

About Ivacaftor

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,
ivacaftor 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. Ivacaftor (150mg, q12h) was first approved by the U.S. Food
and Drug Administration in January 2012, by the European Medicines Agency in
July 2012 and by Health Canada in November 2012 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 ivacaftor. A
Marketing Authorization application is under review by the Therapeutic Goods
Administration (TGA) of Australia.

Indication and Important Safety Information

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 CF patients with two 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.

High 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. Moderate transaminase
elevations are common in subjects with CF. Overall, the incidence and clinical
features of transaminase elevations in clinical trials was similar between
subjects in the ivacaftor and placebo treatment groups. In the subset of
patients with a medical history of elevated transaminases, increased ALT or
AST have been reported more frequently in patients receiving ivacaftor
compared to placebo.

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 concomitantly used 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 full product labeling for each country where ivacaftor is
approved. Patients should tell their healthcare providers about any side
effect that bothers them or doesn't go away.

Please see full U.S. Prescribing Information for KALYDECO,
the EU Summary of Product Characteristics for KALYDECO at,
and the KALYDECO Canadian Product Monograph at

About Cystic Fibrosis

Cystic fibrosis is a rare, life-shortening 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 nearly 3,000 in Australia.
Today, the median predicted age of survival for a person with CF is
approximately 37 years in the United States, about 40 years in Europe and 48
years in Canada, but the median age of death remains in the mid-20s.

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 non-profit drug discovery and development affiliate of the
Cystic Fibrosis Foundation in the U.S. 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, (i) the expectation that reimbursement in Ireland for ivacaftor
will start in the second quarter of 2013 and (ii) the statements by Mr. Bedson
in the third paragraph of this press release. 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 the 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
Megan Goulart, 617-341-6992
Nikki Levy, 617-341-6992
Michael Partridge, 617-341-6108
Kelly Lewis, 617-961-7530
Press spacebar to pause and continue. Press esc to stop.