Market Overview

Vertex Receives European CHMP Positive Opinion for SYMKEVI® (tezacaftor/ivacaftor) for People with Cystic Fibrosis Aged 12 and Older with Certain Mutations in the CFTR Gene

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If approved, SYMKEVI® (tezacaftor/ivacaftor)
will be Vertex's third medicine to treat the CFTR protein defect in
patients with cystic fibrosis – a rare life-shortening disease

Vertex Pharmaceuticals (Europe) Limited, today announced that the
European Medicines Agency's (EMA) Committee for Medicinal Products for
Human Use (CHMP) adopted a positive opinion for SYMKEVI®
(tezacaftor/ivacaftor) in a combination regimen with ivacaftor (KALYDECO®)
for the treatment of people with cystic fibrosis (CF) aged 12 and older
who either have two copies of the F508del mutation in the cystic
fibrosis transmembrane conductance regulator (CFTR) gene, or one copy of
the F508del mutation and a copy of one of the following 14
mutations in which the CFTR protein shows residual activity: P67L,
R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W,
D1152H, 2789+5G→A, 3272-26A→G,
and 3849+10kbC→T.

If granted Marketing Authorization by the European Commission (EC),
tezacaftor/ivacaftor will be used in combination with
ivacaftor and will be the first medicine to treat the CFTR protein
defect in CF patients who have one copy of the F508del mutation
and a copy of one of 14 mutations that result in residual CTFR activity.
It also provides a new treatment option for a significant number of
people living with CF who have two copies of the F508del mutation.

"Our goal at Vertex is to find a cure for all people living with CF and
we are moving rapidly towards treating up to 90 percent of patients,"
said Reshma Kewalramani, MD, Executive Vice President, Global Medicines
Development and Medical Affairs and Chief Medical Officer at Vertex.
"Today's announcement is a pivotal accomplishment along that journey. If
approved, tezacaftor/ivacaftor in combination with ivacaftor represents
an important option for people with two copies of the F508del
mutation and the first medicine in the EU for patients with one copy of
the F508del mutation and a copy of one of 14 mutations that
result in residual CTFR activity."

The regulatory submission was supported by results from two pivotal
Phase 3 studies, EVOLVE and EXPAND, published in the New England
Journal of Medicine
in November 2017. Results showed treatment with
tezacaftor/ivacaftor in combination with ivacaftor provides benefits
across different CF populations, including statistically significant
improvements in lung function, as determined by absolute change from
baseline in ppFEV1, and with a generally well tolerated
safety profile and a lack of increased respiratory adverse events
compared to placebo. The most common adverse reactions experienced by
patients who received tezacaftor/ivacaftor in combination with ivacaftor
in pooled, placebo-controlled Phase 3 studies were headache and
nasopharyngitis.

"Tezacaftor/ivacaftor combination therapy for CF is another important
achievement in the development of disease modulating therapies. This
combination improves important clinical outcomes and may benefit those
who cannot use ORKAMBI® (lumacaftor/ivacaftor)," said
Professor Stuart Elborn, Clinical Professor of Respiratory Medicine, and
Centre Director for Specialist Adult Cystic Fibrosis at the Royal
Brompton Hospital, London.

Tezacaftor/ivacaftor in combination with ivacaftor was approved by the
U.S. Food and Drug Administration (FDA) in February 2018 and by Health
Canada in June 2018. It is marketed as SYMDEKO™ in the U.S. and Canada.

About CF

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

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 approximately 2,000
known mutations in the CFTR gene. Some of these mutations, which
can be determined by a genetic test, or genotyping test, lead to CF by
creating non-working or too few CFTR proteins at the cell surface. The
defective function or absence of CFTR protein results in poor flow of
salt and water into and out of the cell in a number of organs. In the
lungs, this leads to the build-up 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 age of death is in
the mid-to-late 20s.

About tezacaftor/ivacaftor and ivacaftor

Some mutations result in CFTR protein that is not processed or folded
normally within the cell, and that generally does not reach the cell
surface. Tezacaftor is designed to address the trafficking and
processing defect of the CFTR protein to enable it to reach the cell
surface where ivacaftor can increase the amount of time the protein
stays open.

About EVOLVE and EXPAND

Data from the two Phase 3 studies EVOLVE and EXPAND were published
in the New England Journal of Medicine in November 2017, the
studies enrolled approximately 750 people with CF ages 12 and older with
two copies of the F508del mutation or with one F508del
mutation and second mutation that is responsive to tezacaftor/ivacaftor.
Across both studies, patients treated with tezacaftor/ivacaftor in
combination with ivacaftor experienced statistically significant
improvements in lung function, as determined by absolute change from
baseline in percent predicted forced expiratory volume in one second
(ppFEV1). The treatment was generally well tolerated; the
most common adverse reactions (≥10%) experienced by patients who
received tezacaftor/ivacaftor with ivacaftor in the pooled,
placebo-controlled Phase 3 studies were headache (14% versus 12% on
placebo) and nasopharyngitis (12% versus 10% on placebo).

About Vertex

Vertex is a global biotechnology company that invests in scientific
innovation to create transformative medicines for people with serious
and life-threatening diseases. In addition to clinical development
programs in CF, Vertex has more than a dozen ongoing research programs
focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Mass., Vertex's headquarters is now
located in Boston's Innovation District. Today, the company has research
and development sites and commercial offices in the United States,
Europe, Canada and Australia. Vertex is consistently recognized as one
of the industry's top places to work, including being named to Science
magazine's Top Employers in the life sciences ranking for eight years in
a row. For additional information and the latest updates from the
company, please visit www.vrtx.com.

(VRTX-GEN)

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