Market Overview

Vertex Receives Approval for SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) in Australia, to Treat the Underlying Cause of Cystic Fibrosis in People aged 12 and Older with Certain CFTR Gene Mutations

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-A new treatment option for patients with two copies of the F508del
mutation, the most common mutation in cystic fibrosis-

-First medicine in Australia to treat the underlying cause of cystic
fibrosis in patients who have certain mutations that result in residual
CFTR function-

Vertex
Pharmaceuticals Incorporated
today announced that the Therapeutic
Goods Administration (TGA) of Australia has granted registration to
SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) for the
treatment of people with cystic fibrosis (CF) aged 12 years and older
who are homozygous for the F508del mutation or who have at least
one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR)
gene that is responsive to tezacaftor/ivacaftor based on in vitro
data and/or clinical evidence. Mutations in the CFTR gene that
produce CFTR protein responsive to SYMDEKO® include
F508del
and mutations in which the CFTR protein shows residual
function: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L,
S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, 3849+10kbC→T, E56K, R74W,
D110E, D110H, E193K, E831X, F1052V, K1060T, A1067T, F1074L and D1270N
.
SYMDEKO® will be considered for Australian reimbursement for
eligible CF patients aged 12 years and older at the March meeting of the
Pharmaceutical Benefits Advisory Committee.

"We are delighted that the Therapeutic Goods Administration in Australia
recognized the safety profile and efficacy of SYMDEKO®. This
approval brings us one step closer to our future goal of bringing
treatment to all people living with CF," said Reshma Kewalramani, M.D.,
Executive Vice President and Chief Medical Officer at Vertex. "This new
medicine is an especially important treatment option for patients with
residual function mutations and those with two copies of the F508del
mutation who either never started or discontinued ORKAMBI®
(lumacaftor/ivacaftor)."

The TGA's decision is based on 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 percent
predicted forced expiratory volume in one second (ppFEV1),
with a generally well tolerated safety profile and a lack of increased
respiratory adverse events compared to placebo. The improvements in lung
function showed a mean absolute change in ppFEV1 compared to
placebo of 4.0 percentage points (P<0.0001) and 6.8 percentage
points (P<0.0001) in EVOLVE and EXPAND respectively. The most
common adverse reactions (≥10% incidence) experienced by patients who
received tezacaftor/ivacaftor in combination with ivacaftor in pooled,
placebo-controlled Phase 3 studies were headache and nasopharyngitis.

Tezacaftor/ivacaftor in combination with ivacaftor was approved by the
U.S. Food and Drug Administration (FDA) in February 2018, by Health
Canada in June 2018 and by the European Commission in October 2018.

About Cystic Fibrosis

Cystic Fibrosis (CF) 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 cystic fibrosis transmembrane
conductance regulator (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 buildup 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 SYMDEKO® (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. SYMDEKO is a combination of tezacaftor and ivacaftor.
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.

U.S. INDICATION AND IMPORTANT SAFETY INFORMATION FOR SYMDEKO®
(tezacaftor/ivacaftor and ivacaftor) tablets:

SYMDEKO is a prescription medicine used for the treatment of cystic
fibrosis (CF) in patients aged 12 years and older who have two copies of
the F508del mutation, or who have at least one mutation in the CF
gene that is responsive to treatment with SYMDEKO. Patients should talk
to their doctor to learn if they have an indicated CF gene mutation. It
is not known if SYMDEKO is safe and effective in children under 12 years
of age.

Patients should not take SYMDEKO if they take certain medicines or
herbal supplements such as:
the antibiotics rifampin or rifabutin;
seizure medicines such as phenobarbital, carbamazepine, or phenytoin;
St. John's wort.

Before taking SYMDEKO, patients should tell their doctor if they: have
or have had liver problems; have kidney problems; are pregnant or plan
to become pregnant because it is not known if SYMDEKO will harm an
unborn baby; are breastfeeding or planning to breastfeed because it is
not known if SYMDEKO passes into breast milk.

SYMDEKO may affect the way other medicines work, and other medicines
may affect how SYMDEKO works.
Therefore, the dose of SYMDEKO may
need to be adjusted when taken with certain medicines. Patients should
especially tell their doctor if they take antifungal medicines such as
ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole;
or antibiotics such as telithromycin, clarithromycin, or erythromycin.

SYMDEKO may cause dizziness in some people who take it. Patients
should not drive a car, use machinery, or do anything that requires
alertness until they know how SYMDEKO affects them.

Patients should avoid food or drink that contains grapefruit or
Seville oranges while they are taking SYMDEKO.

SYMDEKO can cause serious side effects, including:

High liver enzymes in the blood, which have been reported in
people treated with SYMDEKO or treated with ivacaftor alone. The
patient's doctor will do blood tests to check their liver before they
start SYMDEKO, every 3 months during the first year of taking SYMDEKO,
and every year while taking SYMDEKO. Patients should call their doctor
right away if they have any of the following symptoms of liver problems:
pain or discomfort in the upper right stomach (abdominal) area;
yellowing of the skin or the white part of the eyes; loss of appetite;
nausea or vomiting; dark, amber-colored urine.

Abnormality of the eye lens (cataract) in some children and
adolescents treated with SYMDEKO or with ivacaftor alone. If the patient
is a child or adolescent, their doctor should perform eye examinations
before and during treatment with SYMDEKO to look for cataracts.

The most common side effects of SYMDEKO include headache, nausea,
sinus congestion, and dizziness.

These are not all the possible side effects of SYMDEKO. Please click here
to see the full
U.S. Prescribing Information for SYMDEKO
(tezacaftor/ivacaftor and ivacaftor) tablets.

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 a second mutation associated with residual CFTR activity.
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 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, Australia and Latin America. 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 nine years in a row. For additional information and the
latest updates from the company, please visit www.vrtx.com.

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, the expected March meeting of the Pharmaceuticals Benefits
Advisory Committee and the quote by Dr. Kewalramani in the second
paragraph. 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 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 www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.

(VRTX-GEN)

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