- Study met primary endpoint with a
statistically significant improvement in absolute change in lung
clearance index (LCI2.5) compared to placebo through 24 weeks of
treatment -
- ORKAMBI was well tolerated with safety data
that were similar to data from previous Phase 3 open-label safety
study -
- Approximately 3,400 children ages 6-11 have
two copies of the F508del mutation in Europe -
Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) today
announced the results of a Phase 3 study of ORKAMBI®
(lumacaftor/ivacaftor) in children with cystic fibrosis (CF) ages 6
through 11 who have two copies of the F508del mutation. 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 patients
treated with ORKAMBI compared to placebo. LCI is a sensitive
measure of lung function in early CF disease and the European
Medicines Agency (EMA) agreed to the primary endpoint for this
study. In the first half of 2017, Vertex plans to submit a
Marketing Authorization Application (MAA) line extension to the EMA
for the use of ORKAMBI in this patient population. Data from a
previous Phase 3 open-label safety study in children ages 6 through
11 supported the U.S. Food and Drug Administration approval of
ORKAMBI in September 2016. In this second study, ORKAMBI was well
tolerated with safety data that were similar to data from the
previous Phase 3 study. There are approximately 3,400 children ages
6 through 11 who have two copies of the F508del mutation in
Europe.
“This study is an important complement to recently presented
long-term data in patients 12 years and older suggesting ORKAMBI
may modify the course of CF. These new data demonstrate that
treating the underlying cause of the disease with ORKAMBI improves
lung function in even younger patients,” said Jeffrey Chodakewitz,
M.D., Executive Vice President and Chief Medical Officer at Vertex.
“We are preparing to submit these important data to the EMA in the
first half of 2017, and we look forward to bringing ORKAMBI to
eligible children in Europe as soon as possible.”
“CF is a progressive disease that begins at birth, and
traditional measurements do not always detect the early lung damage
that occurs in children,” said Felix Ratjen, M.D., Division Chief
of Pediatric Respiratory Medicine at The Hospital for Sick Children
Toronto, Professor of Pediatrics at The University of Toronto, a
Senior Scientist at the Research Institute in the Department of
Physiology and Experimental Medicine, and Principal Investigator
for the study. “LCI is a sensitive measure of lung function, and
these new data demonstrate that treating children early with
ORKAMBI can improve lung function.”
Summary of Key Data
The data announced today are from a Phase 3, randomized,
double-blind, placebo-controlled, parallel-group, multicenter study
to evaluate the efficacy and safety of ORKAMBI in children ages 6
through 11 who have two copies of the F508del mutation. The study
compared children who received treatment with lumacaftor (200 mg
q12h) in combination with ivacaftor (250 mg q12h) (n=103) with
those who received placebo (n=101) for 24 weeks. Baseline lung
function as measured by percent predicted forced expiratory volume
in one second (ppFEV1) was 89.8.
The primary endpoint of the study was absolute change in lung
clearance index (LCI2.5) from baseline through Week 24. LCI2.5
measures the efficiency of ventilation in the lungs by quantifying
how long it takes to reduce an inhaled tracer gas to 2.5 percent of
its starting value. 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 had to have an LCI2.5 ≥7.5 at
the initial screening visit, considered the cutoff for abnormal gas
exchange. At baseline, mean LCI2.5 was 10.28. In the study,
children treated with ORKAMBI experienced an improvement in lung
function (LCI2.5) of -1.09 compared to placebo through 24 weeks
(p<0.0001).
Improvements in secondary endpoints were also observed in this
study, including a statistically significant reduction in sweat
chloride assessed by the average absolute change from baseline at
Day 15 and Week 4 (-20.8 mmol/L compared to placebo; p<0.0001).
Improvements in body mass index (BMI) and the Cystic Fibrosis
Questionnaire-Revised (CFQ-R) respiratory domain score were also
observed, although not statistically significant. The improvement
in absolute change from baseline in body mass index (BMI) at Week
24 was 0.11 kg/m2 compared to placebo (p=0.2522) and the
improvement in absolute change from baseline in CFQ-R respiratory
domain score through Week 24 was 2.5 points compared to placebo
(p=0.0628). Lung function as assessed by an absolute change from
baseline in ppFEV1 through Week 24 was an additional endpoint of
the study for which a statistically significant improvement of 2.4
percentage points compared to placebo (p=0.0182) was observed.
Overall, safety data were similar to those observed in a
previous Phase 3 open-label safety study in children ages 6 through
11. In this 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. Treatment discontinuations due to adverse events were
low across those receiving placebo (n=2) and those receiving
ORKAMBI (n=3) through 24 weeks.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR
ORKAMBI® (lumacaftor/ivacaftor) TABLETS
ORKAMBI is a prescription medicine used for the treatment of
cystic fibrosis (CF) in patients age 6 years and older who have two
copies of the F508del mutation (F508del/F508del) in their CFTR
gene. ORKAMBI should only be used in these patients. It is not
known if ORKAMBI is safe and effective in children under 6 years of
age.
Patients should not take ORKAMBI if they are taking certain
medicines or herbal supplements, such as: the antibiotics
rifampin or rifabutin; the seizure medicines phenobarbital,
carbamazepine, or phenytoin; the sedatives/anti-anxiety medicines
triazolam or midazolam; the immunosuppressant medicines everolimus,
sirolimus, or tacrolimus; or St. John’s wort.
Before taking ORKAMBI, patients should tell their doctor if
they: have or have had liver problems; have kidney problems;
have had an organ transplant; are using birth control (hormonal
contraceptives, including oral, injectable, transdermal or
implantable forms). Hormonal contraceptives should not be used as a
method of birth control when taking ORKAMBI. Patients should tell
their doctor if they are pregnant or plan to become pregnant (it is
unknown if ORKAMBI will harm the unborn baby) or if they are
breastfeeding or planning to breastfeed (it is unknown if ORKAMBI
passes into breast milk).
ORKAMBI may affect the way other medicines work and other
medicines may affect how ORKAMBI works. Therefore, the dose of
ORKAMBI or other medicines may need to be adjusted when taken
together. Patients should especially tell their doctor if they
take: antifungal medicines such as ketoconazole, itraconazole,
posaconazole, or voriconazole; or antibiotics such as
telithromycin, clarithromycin, or erythromycin.
When taking ORKAMBI, patients should tell their doctor if
they stop ORKAMBI for more than 1 week as the doctor may need to
change the dose of ORKAMBI or other medicines the patient is
taking. It is unknown if ORKAMBI causes dizziness. Patients should
not drive a car, use machinery, or do anything requiring alertness
until the patient knows how ORKAMBI affects them.
ORKAMBI can cause serious side effects including:
High liver enzymes in the blood, which can be a sign of liver
injury, have been reported in patients receiving ORKAMBI. The
patient’s doctor will do blood tests to check their liver before
they start ORKAMBI, every three months during the first year of
taking ORKAMBI, and annually thereafter. The patient should call
the 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; or confusion.
Respiratory events such as shortness of breath or chest
tightness were observed in patients when starting ORKAMBI. If a
patient has poor lung function, their doctor may monitor them more
closely when starting ORKAMBI.
An increase in blood pressure has been seen in some patients
treated with ORKAMBI. The patient’s doctor should monitor their
blood pressure during treatment with ORKAMBI.
Abnormality of the eye lens (cataract) has been noted in some
children and adolescents receiving ORKAMBI and ivacaftor, a
component of ORKAMBI. For children and adolescents, the
patient’s doctor should perform eye examinations prior to and
during treatment with ORKAMBI to look for cataracts.
The most common side effects of ORKAMBI include: shortness of
breath and/or chest tightness; upper respiratory tract infection
(common cold), including sore throat, stuffy or runny nose;
gastrointestinal symptoms including nausea, diarrhea, or gas; rash;
fatigue; flu or flu-like symptoms; increase in muscle enzyme
levels; and irregular, missed, or abnormal menstrual periods and
heavier bleeding.
Please click here to see the full Prescribing
Information for ORKAMBI.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening 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, lead to CF by creating defective or
too few CFTR proteins at the cell surface. The defective or missing
CFTR protein results in poor flow of salt and water into or 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 in many
patients that eventually leads to death. The median predicted age
of survival for a person born today with CF is 41 years, but the
median age of death is 27 years.
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
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) and ORKAMBI (lumacaftor/ivacaftor) 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 from Dr. Chodakewitz
and Dr. Ratjen and statements regarding Vertex’s plans to submit a
Marketing Authorization Application line extension to the EMA.
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
ORKAMBI or its other 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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Vertex Pharmaceuticals
IncorporatedInvestors:Michael Partridge,
617-341-6108orEric Rojas, 617-961-7205orZach Barber,
617-341-6470orMedia: mediainfo@vrtx.comNorth
America:Chris Stamm, +1 617-341-6992orEurope & Australia:Megan
Goulart, +44 20 3204 5275
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