Positive Phase 3 Study for Tezacaftor/Ivacaftor Combination in Children Aged 6-11 Years with Cystic Fibrosis Supports European Medicines Agency Submission

-Study met primary endpoint with a statistically significant
improvement in absolute change in lung clearance index (LCI
2.5)
through 8 weeks of tezacaftor/ivacaftor treatment-

-Tezacaftor in combination with ivacaftor was generally well
tolerated and safety data were consistent with previous studies-

-Data support a submission to the European Medicines Agency in the
second half of 2019-

BOSTON–(BUSINESS WIRE)–Vertex
Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced the
results of a Phase 3 study conducted in Europe and Australia of
tezacaftor in combination with ivacaftor in children aged 6 through 11
years with cystic fibrosis (CF) who have either two copies of the F508del
mutation or one copy of the F508del mutation and one residual
function mutation. The study met its primary endpoint of absolute change
in lung clearance index (LCI2.5) through 8 weeks of
treatment, demonstrating a statistically significant improvement in LCI2.5
among patients treated with tezacaftor/ivacaftor. The regimen was
generally well tolerated and safety data were consistent with those
observed in previous studies with tezacaftor/ivacaftor. This efficacy
study was designed to support a submission to the European Medicines
Agency (EMA) to extend the indication of tezacaftor/ivacaftor in this
patient population. Vertex plans to submit the application in the second
half of 2019. In late 2018, Vertex submitted an sNDA to the U.S. Food
and Drug Administration (FDA) for tezacaftor/ivacaftor based on a
previously completed Phase 3 safety study in children ages 6 through 11
years of age conducted in the U.S. and Canada.

“These data mark an important milestone in our efforts to expand
treatment options for patients living with CF,” said Reshma Kewalramani,
M.D., Executive Vice President and Chief Medical Officer at Vertex. “We
plan to submit an indication extension to the EMA in the second half of
2019, bringing us a step closer to potentially providing more children
with a treatment option that addresses the underlying cause of the
disease.”

Summary of Key Data

The data announced today are from a Phase 3, randomized, double-blind,
parallel-group study to evaluate the efficacy and safety of tezacaftor
in combination with ivacaftor in children ages 6 through 11 who have
either two copies of the F508del mutation or one copy of the F508del
mutation and one residual function mutation. Subjects were randomized
4:1 based on their genotype to tezacaftor/ivacaftor versus a blinding
arm (placebo for those with two copies of F508del; ivacaftor for
those with one copy of F508del mutation and one residual function
mutation). The study randomized and treated 54 subjects with TEZ/IVA, 10
with placebo, and 3 with ivacaftor.

The primary endpoint of the study was the within-group absolute change
in lung clearance index (LCI2.5) from baseline through Week 8
in patients treated with tezacaftor/ivacaftor. LCI2.5
measures the efficiency of ventilation in the lungs by quantifying how
many standard lung volumes it takes to reduce exhaled nitrogen to 2.5
percent of its starting value when breathing pure oxygen. LCI is
considered a more sensitive measure to detect early lung disease than
forced expiratory volume in one second (FEV1). Higher LCI
scores indicate poorer lung function. To participate in the study,
children at an initial screening visit had to have an LCI2.5 ≥7.5,
which is considered the cutoff for abnormal gas exchange. In the study,
54 children that were treated with tezacaftor/ivacaftor experienced a
mean within-group absolute improvement in LCI2.5 of -0.51
through 8 weeks (p < 0.0001).

Overall, safety data were similar to those observed in previous studies
of tezacaftor/ivacaftor. The most common adverse events (≥ 10%) among
those patients receiving tezacaftor/ivacaftor were cough, headache, and
productive cough. No serious adverse events or adverse events leading to
treatment discontinuation or interruption were observed.

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 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.

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), SYMDEKO®
(tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 were discovered
by Vertex as part of this collaboration.

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 statements in the first paragraph of the press release
and 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)

Contacts

Vertex Pharmaceuticals Incorporated
Investors:
Michael
Partridge, 617-341-6108
or
Eric Rojas, 617-961-7205
or
Zach
Barber, 617-341-6470
or
Media:
[email protected]
or
North
America: + 1-617-341-6992
or
Europe & Australia: + 44 20 3204
5275

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