Market Overview

Vertex Announces Nine Presentations of Data on ORKAMBI® (lumacaftor/ivacaftor) and KALYDECO® (ivacaftor) at the European Cystic Fibrosis Society (ECFS) Conference


Pharmaceuticals Incorporated
(NASDAQ:VRTX) today announced nine
presentations of data on ORKAMBI® (lumacaftor/ivacaftor) and
KALYDECO® (ivacaftor) at the 40th European Cystic
Fibrosis Society (ECFS) Conference, being held June 7-10, 2017. Data
from a Phase 3 placebo-controlled study of ORKAMBI in children with
cystic fibrosis (CF) ages 6 through 11 who have two copies of the F508del
mutation were presented at the meeting and published online today in The
Lancet Respiratory Medicine
. In addition, results from a study of
ORKAMBI in people ages 12 and older who have two copies of the F508del
mutation and advanced lung disease as well as a post-hoc analysis of
long-term use of ORKAMBI in three Phase 3 studies were also presented at
the meeting. The data presented at the Conference demonstrate that
treating the underlying cause of CF with CFTR modulators can modify the
progression of the disease.

"In nearly 20 years of research in collaboration with the cystic
fibrosis community, we've made remarkable progress in efforts to change
the way CF is treated by developing medicines that address the
underlying cause of the disease, not just the symptoms," said Jeffrey
Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at
Vertex. "Thousands of patients around the world are benefitting from
KALYDECO and ORKAMBI, which have both shown the ability to modify the
progression of CF. The data presented at this meeting further
demonstrate that treatment with CFTR modulators can deliver early and
sustained benefits for eligible patients."

ORKAMBI in children ages 6 to 11 ("Efficacy and safety of
lumacaftor/ivacaftor in patients aged 6-11 years with cystic fibrosis
homozygous for F508del-CFTR: a randomized placebo-controlled
Phase 3 trial." WS13.4.)

Data were presented for the first time from a Phase 3 randomized,
double-blind, placebo-controlled study that evaluated ORKAMBI in 204
children with CF ages 6 through 11 who have two copies of the F508del
mutation. At the start of the study, the average baseline predicted
forced expiratory volume in one second (ppFEV1) was
approximately 90. In the study, all children received a twice-daily
fixed-dose combination of lumacaftor (200mg) and ivacaftor (250mg) for
24 weeks. As announced in November
, the study met its primary endpoint of absolute change in lung
clearance index (LCI2.5) through 24 weeks of treatment,
demonstrating a statistically significant improvement in LCI2.5
among those treated with ORKAMBI compared to placebo. The study also
demonstrated significant improvements in ppFEV1 and sweat
chloride in children receiving ORKAMBI compared with those receiving

Overall, safety data were similar to those observed in a previous Phase
3 open-label safety study in children ages 6 through 11. In the
placebo-controlled study, the most common adverse events that occurred
more frequently among those receiving ORKAMBI compared to placebo were
infective pulmonary exacerbation, productive cough, nasal congestion,
oropharyngeal pain, abdominal pain upper, headache, upper respiratory
tract infection and sputum increased. The incidence of liver enzyme
elevations and respiratory events were slightly higher in the ORKAMBI
group compared to placebo. Respiratory events were mild to moderate in
severity and the majority were resolved without interrupting treatment.
Treatment discontinuations due to adverse events were low across those
receiving placebo (n=2) and those receiving ORKAMBI (n=3) through 24

Additional details from the study will be presented at ECFS as part of Workshop
13, New therapies targeting CFTR: what's new from the clinical trials
and as part of an invited talk during Symposium 22,
Best of Journal of Cystic Fibrosis and The Lancet Respiratory Medicine
. The data were also published online
today in The Lancet Respiratory Medicine.

In the U.S., ORKAMBI was approved in September 2016 for use in children
with CF ages 6 through 11 who have two copies of the F508del
mutation. In the EU, Vertex submitted a Marketing Authorization
Application (MAA) line extension in March 2017 for the use of ORKAMBI in
these children.

ORKAMBI in advanced lung disease ("Lumacaftor/ivacaftor in
patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR:
a 24-week open-label study." Poster 55.)

Data were presented for the first time from a Phase 3b open-label study
that evaluated ORKAMBI in people with CF ages 12 and older who have two
copies of the F508del mutation and advanced lung disease, defined
as ppFEV1 less than 40 at screening. At the start of the
24-week study, the average baseline ppFEV1 was 29.1. Overall,
the incidence of respiratory adverse events was higher than in other
studies of patients who had higher baseline ppFEV1. Aside
from respiratory adverse events, the safety profile of ORKAMBI seen in
the study was generally consistent with the established safety profile
from other Phase 3 studies.

In the study, a subset of eighteen patients initiated treatment with a
half-dose of ORKAMBI (lumacaftor 200mg q12h / ivacaftor 125mg q12h) for
one to two weeks and then transitioned to the full dose (lumacaftor
400mg q12h / ivacaftor 125mg q12h). An analysis of data from this study
showed that these patients had a lower incidence and shorter duration of
respiratory adverse events compared to those who initiated treatment on
the full dose.

Correlation between Rate of Lung Function Decline and Acute
Improvements in Lung Function with ORKAMBI
between rate of percent predicted FEV1 decline and baseline
and acute change in percent predicted FEV1 in patients with
cystic fibrosis treated with lumacaftor/ivacaftor." Poster 54.)

Progressive loss of lung function is the leading cause of death in
people with CF; therefore, slowing the decline of lung function is a key
goal of CF treatment. As previously reported, up to 120 weeks of ORKAMBI
treatment in the Phase 3 TRAFFIC, TRANSPORT and PROGRESS studies
resulted in a reduced annual rate of ppFEV1 decline and mean
ppFEV1 that remained above baseline. A post-hoc analysis of
these studies evaluated whether there is any correlation between acute
improvement in lung function and the long-term rate of lung function
decline. Results presented at the meeting showed that treatment with
ORKAMBI produces two effects on lung function – an acute improvement in
ppFEV1 and a reduced rate of decline over the long term. The
magnitude of the acute improvement was not correlated with the reduction
in the rate of lung function decline. These data, together with similar
results previously reported for KALYDECO in patients with the G551D
mutation, suggest that baseline ppFEV1 or the magnitude of
acute ppFEV1 change are not predictors of the potential for
disease modification, measured in this case by a reduced rate of decline
in ppFEV1, with CFTR modulation.

Vertex continues to progress its CF development program.
The company is on track to submit a New Drug Application to the U.S.
Food and Drug Administration and an MAA to the European Medicines Agency
in the third quarter of 2017 for the tezacaftor/ivacaftor combination
treatment in people with CF ages 12 and older who have two copies of the F508del
mutation and in people who have one mutation that results in residual
CFTR function and one F508del mutation. In addition, studies
evaluating four different next-generation correctors in combination with
tezacaftor and ivacaftor are underway. Data in people with CF are
expected in the second half of 2017 for the studies evaluating the
next-generation correctors VX-440, VX-152 and VX-659 as part of triple
combination regimens with tezacaftor and ivacaftor.

About ORKAMBI® (lumacaftor/ivacaftor)

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. It is an oral pill taken every 12
hours - once in the morning and once in the evening.

For complete product information, please see the Summary of Product
Characteristics that can be found on

About KALYDECO® (ivacaftor)

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, 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.

For complete product information, please see the Summary of Product
Characteristics that can be found on

About Cystic Fibrosis

Cystic fibrosis is a rare, life-shortening 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

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 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) and tezacaftor
were 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 seven 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

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. Chodakewitz's statements in the second paragraph of the
press release and statements regarding the expected timing of (i)
regulatory applications, including NDAs, MAAs and MAA line extensions
and (ii) the expected timing, clinical trial designs and results for
ongoing clinical studies of next-generation correctors in combination
with tezacaftor and ivacaftor. While Vertex 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 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
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.


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