- Data from ongoing extension study of ORKAMBI®
(lumacaftor/ivacaftor) in children ages 6-11 and real-world
KALYDECO® (ivacaftor) data demonstrate long-term safety and other
benefits of these medicines -
- New data from ongoing extension study of
tezacaftor/ivacaftor combination demonstrate sustained benefits up
to 48 total weeks of treatment -
- First presentation of previously announced
early data from Phase 1 and Phase 2 studies of three different
triple combination regimens -
Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) today
announced presentations of data at the Annual North American Cystic
Fibrosis Conference (NACFC), November 2 to 4, 2017, in
Indianapolis, from across the company’s portfolio of cystic
fibrosis (CF) medicines and medicines in development that
demonstrate important progress toward the company’s goal of helping
all people with CF. Key presentations highlight the acute and
long-term benefits of CFTR modulation, including data from an
ongoing extension study of ORKAMBI® (lumacaftor/ivacaftor) showing
that improvements in lung function and other measures of disease
were maintained through 48 weeks in children with CF ages 6 to 11
who have two copies of the F508del mutation, and real-world data
demonstrating the impact of KALYDECO® (ivacaftor) across multiple
CF measures in slowing disease progression. Also being presented at
the Conference are new data from an ongoing extension study of the
tezacaftor/ivacaftor combination demonstrating sustained benefits
for up to 48 total weeks of treatment, and the first presentation
of previously announced data from Phase 1 and Phase 2 studies of
three different triple combination regimens.
“The breadth of data presented at this meeting demonstrate
significant progress toward our key goals of bringing
disease-modifying medicines to all people with CF and increasing
the benefits for patients on our current medicines,” said Jeffrey
Chodakewitz, M.D., Executive Vice President and Chief Medical
Officer at Vertex. “We also know that many people with CF are still
waiting for a medicine to treat the cause of their disease and we
are continuing our efforts to develop additional new medicines,
such as triple combination regimens, for these people with a sense
of urgency.”
ORKAMBI in Children Ages 6 to 11
“Safety and Efficacy of Lumacaftor/Ivacaftor (LUM/IVA) in
Patients aged ≥6 years with CF Homozygous for F508del-CFTR (Phase 3
Extension Study).” Poster 278.
Two hundred and forty children ages 6 to 11 who have two copies
of the F508del mutation and who completed 24 weeks of treatment in
either the Phase 3 randomized, double-blind, placebo-controlled
ORKAMBI study (designed to support approval in the EU) or the
open-label Phase 3 ORKAMBI safety study (designed to support
approval in the U.S.) entered a Phase 3 rollover study to receive
ORKAMBI for an additional 96 weeks. A pre-planned interim analysis
was conducted once all participants completed 24 weeks in the
rollover study for a total of 48 total weeks of ORKAMBI treatment
(48 weeks for those who received ORKAMBI in the placebo-controlled
study or in the open-label study; 24 weeks for those who received
placebo in the placebo-controlled study).
This analysis showed that the improvements over baseline in lung
function (measured by the absolute change in lung clearance index,
or LCI2.5), sweat chloride and body mass index (BMI) were
maintained through 48 weeks of treatment. In addition, the pattern
and magnitude of response observed after the initiation of ORKAMBI
in children who previously received placebo were similar to those
seen among children who received ORKAMBI in the initial
studies.
Safety data from this interim analysis were similar to those
observed in previous Phase 3 studies in children ages 6 to 11. Most
adverse events were mild or moderate. Six patients discontinued
treatment due to adverse events (3 due liver enzyme elevations, 1
due to autoimmune hepatitis, 1 due to a gastrointestinal disorder
and 1 due to urticaria (hives)). The most common adverse events
(≥15%) were cough, infective pulmonary exacerbation, pyrexia
(fever), nasal congestion, headache and upper respiratory tract
infection. Serious adverse events were reported in 40 patients
(17%). Predefined respiratory events were observed more frequently
in those who previously received placebo compared to those who
continued ORKAMBI treatment (19.8% vs 8.4%); all were mild or
moderate, and none led to treatment discontinuation. Six patients
(2.5%) experienced elevated liver enzymes of greater than eight
times the upper limit of normal. Of the three patients who
discontinued treatment due to elevated liver enzymes, all levels
returned to baseline after stopping treatment.
“Cystic fibrosis is a progressive disease where the damage
begins at birth,” said Mark Chilvers, M.D., lead investigator for
the rollover study, BC Children’s Hospital, Clinical Associate
Professor, Division of Respiratory Medicine, Department of
Pediatrics, Faculty of Medicine, University of British Columbia.
“Because of this, it is critical to begin treating the disease as
early as possible. These data are important because they
demonstrate that in children as young as 6 years of age, ORKAMBI is
well tolerated and that the respiratory and nutritional changes are
sustained over time.”
“Effect of Lumacaftor/Ivacaftor on Total, Bronchiectasis, and
Air Trapping Computed Tomography (CT) Scores in Children Homozygous
for F508del-CFTR: Exploratory Imaging Substudy.” Poster 197. Oral
presentation during Workshop W18--NT: Innovative Approaches to CF
Therapy.
“Feasibility of Ultrashort Echo Time (UTE) MRI to Evaluate the
Effect of Lumacaftor/Ivacaftor Therapy in Children with Cystic
Fibrosis (CF) Homozygous for F508del.” Poster 266.
CF-related lung disease is known to start before it is
detectable by a decrease in lung function as measured by percent
predicted forced expiratory volume in one second, or ppFEV1. Once
ppFEV1 has fallen below normal, structural lung damage may have
already occurred; much of this can be irreversible.
This exploratory sub-study was conducted in 19 children with CF
ages 6 to 11 who have two copies of the F508del mutation and who
participated in the Phase 3 ORKAMBI study designed to support EU
approval (n=206). An exploratory analysis of CT and MRI scans was
used to evaluate treatment effects in children with CF with mild
lung disease. In the 24-week exploratory analysis, treatment with
ORKAMBI showed positive trends toward improvement in Total Brody
Score, which is a system that evaluates the extent and severity of
structural lung damage. These results demonstrate the potential
utility of CT and MRI for monitoring the treatment effects of CFTR
modulators.
KALYDECO Real-World Outcomes
“Real-World Outcomes in Patients with CF Treated with Ivacaftor:
2015 US and UK CF Registry Analyses.” Poster 496.
“Disease Progression in Patients with CF Treated with Ivacaftor:
Analyses of Real-World Data from the US and UK CF
Registries.” Poster 497.
Interim data collected through 2015 from the ongoing, five-year,
post-approval observational safety study evaluating long-term
outcomes in CF patients on KALYDECO continue to support that
treating the underlying cause of CF has the potential to modify the
course of disease in a real-world setting.
In both the U.S. and UK registries, patients who received
KALYDECO in 2015 had lower risk of death, transplantation,
hospitalizations and pulmonary exacerbations compared to patients
who were matched on age, gender and genotype class who did not
receive KALYDECO. In addition, select CF-related complications were
less common in patients who received KALYDECO. Patients who
received KALYDECO from year one of commercial availability had
consistently better preserved lung function and improved
nutritional measures compared to matched untreated patients. No new
safety concerns were identified. These data further add to the
growing body of evidence showing disease modification by CFTR
modulator treatment.
In total, the analyses included 1,727 patients from the U.S.
Cystic Fibrosis Foundation Patient Registry (CFFPR) and 432
patients from the U.K. Cystic Fibrosis Registry (CFR) who had
received ivacaftor in 2015.
EVOLVE, EXPAND and EXTEND Phase 3 Studies of
Tezacaftor/Ivacaftor
“Efficacy and Safety of Tezacaftor/Ivacaftor in Patients aged
≥12 with CF Homozygous for F508del-CFTR: A Randomized Placebo (PBO)
- Controlled Phase 3 Trial.” Oral presentation S14.1 during
Symposium S14--NT: CF Interventions Advancing Through the Clinical
Testing Phase.
“Efficacy and Safety of Tezacaftor/Ivacaftor in Patients aged
≥12 with CF Heterozygous for F508DEL and a Residual Function
Mutation: A randomized, double-blind, Placebo-Controlled, Crossover
Phase 3 Study.” Oral presentation S14.2 during Symposium S14--NT:
CF Interventions Advancing Through the Clinical Testing Phase.
The first data from the ongoing 96-week EXTEND Phase 3 rollover
study of the tezacaftor/ivacaftor combination were presented during
oral presentations at NACFC. Patients who completed the Phase 3
EVOLVE and EXPAND tezacaftor/ivacaftor studies were eligible to
enter an open-label Phase 3 rollover study, called EXTEND, to
receive tezacaftor/ivacaftor for 96 weeks. This preplanned interim
analysis was conducted when approximately 70 percent of patients
from the EVOLVE study reached 24 weeks in the EXTEND study and when
approximately 70 percent of patients from the EXPAND study reached
16 weeks in the EXTEND study.
This analysis showed that the initial improvements in lung
function (measured by the absolute change in ppFEV1) observed in
the Phase 3 EVOLVE and EXPAND studies were sustained for up to 48
total weeks of treatment (24 weeks in EVOLVE + 24 weeks in EXTEND,
or 8 weeks in EXPAND + 16 weeks in EXTEND). Safety data from this
interim analysis showed that tezacaftor/ivacaftor was generally
well tolerated and had a safety profile consistent with that seen
in EVOLVE and EXPAND.
Triple Combination Regimens
“Preliminary Safety and Efficacy of Triple Combination CFTR
Modulator Regimens in CF.” Poster 777. Oral presentation during
Workshop W18--NT: Innovative Approaches to CF Therapy.
Previously announced data from Phase 1 and Phase 2 studies of
three different next-generation correctors (VX-440, VX-152 and
VX-659) in combination regimens with tezacaftor and ivacaftor were
presented for the first time. These data demonstrate the potential
to treat the underlying cause of CF in people who have one F508del
mutation and one minimal function mutation not responsive to
ivacaftor, tezacaftor or the combination of tezacaftor/ivacaftor, a
severe and difficult-to-treat type of the disease. All studies
showed statistically significant improvements in lung function
(ppFEV1) with a triple combination regimen in these patients. In
addition, initial data from the studies of VX-440 and VX-152 showed
improvements in lung function with the addition of either
next-generation corrector in people with two copies of the F508del
mutation who were already receiving tezacaftor/ivacaftor. The
triple combination regimens were generally well tolerated across
all three studies, and the majority of adverse events were mild to
moderate in severity. Across the studies, the discontinuation rate
due to adverse events was low.
Data from additional ongoing Phase 2 studies are expected in
early 2018. Vertex plans to initiate pivotal development of up to
two triple combination regimens in the first half of 2018.
About Cystic Fibrosis
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 protein 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
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.
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 KALYDECO® (ivacaftor)
KALYDECO (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, KALYDECO is
an oral medicine designed to keep CFTR proteins at the cell surface
open longer to improve the transport of salt and water across the
cell membrane, which helps hydrate and clear mucus from the
airways. KALYDECO is available as 150 mg tablets for adults and
pediatric patients age 6 years and older, and is taken with
fat-containing food. It is also available as 50 mg and 75 mg
granules in pediatric patients ages 2 to less than 6 years and is
administered with soft-food or liquid with fat-containing food.
People with CF who have specific mutations in
the CFTR gene are currently benefiting from KALYDECO in
27 different countries across North
America, Europe and Australia.
KALYDECO® (ivacaftor) INDICATION AND
IMPORTANT SAFETY INFORMATION
KALYDECO (ivacaftor) is a prescription medicine used for the
treatment of cystic fibrosis (CF) in patients age 2 years and older
who have at least one mutation in their CF gene that is responsive
to KALYDECO. Patients should talk to their doctor to learn if they
have an indicated CF gene mutation. It is not known if KALYDECO is
safe and effective in children under 2 years of age.
Patients should not take KALYDECO if they are taking certain
medicines or herbal supplements such as: the antibiotics
rifampin or rifabutin; seizure medications such as phenobarbital,
carbamazepine, or phenytoin; or St. John's wort.
Before taking KALYDECO, patients should tell their doctor if
they: have liver or kidney problems; drink grapefruit
juice, or eat grapefruit or Seville oranges; are pregnant
or plan to become pregnant because it is not known if KALYDECO will
harm an unborn baby; and are breastfeeding or planning to
breastfeed because is not known if KALYDECO passes into breast
milk.
KALYDECO may affect the way other medicines work, and other
medicines may affect how KALYDECO works. Therefore the
dose of KALYDECO may need to be adjusted when taken with certain
medications. Patients should especially tell their doctor if they
take antifungal medications such as ketoconazole, itraconazole,
posaconazole, voriconazole, or fluconazole; or antibiotics such as
telithromycin, clarithromycin, or erythromycin.
KALYDECO can cause dizziness in some people who take it.
Patients should not drive a car, use machinery, or do anything that
needs them to be alert until they know how KALYDECO affects them.
Patients should avoid food containing grapefruit
or Seville oranges while taking KALYDECO.
KALYDECO can cause serious side effects including:
High liver enzymes in the blood have been reported in
patients receiving KALYDECO. The patient's doctor will do
blood tests to check their liver before starting KALYDECO, every 3
months during the first year of taking KALYDECO, and every year
while taking KALYDECO. For patients who have had high liver enzymes
in the past, the doctor may do blood tests to check the liver more
often. 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 their
skin or the white part of their eyes; loss of appetite; nausea or
vomiting; or dark, amber-colored urine.
Abnormality of the eye lens (cataract) has been noted in some
children and adolescents receiving KALYDECO. The patient's doctor
should perform eye examinations prior to and during treatment with
KALYDECO to look for cataracts. The most common side effects
include headache; upper respiratory tract infection (common cold),
which includes sore throat, nasal or sinus congestion, and runny
nose; stomach (abdominal) pain; diarrhea; rash; nausea; and
dizziness.
These are not all the possible side effects of KALYDECO.
Please click here to see the full
Prescribing Information for KALYDECO.
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.
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),
tezacaftor, VX-440, VX-152 and VX-659 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, statements in the second and sixth
paragraphs and statements regarding the timing of and development
plan with respect to the next-generation triple combination
regimens. 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 Vertex could
experience unforeseen delays in conducting its development programs
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.comorNorth America:Megan
Goulart, + 1-617-341-6992orEurope & Australia:Rebecca
Hunt, +44 7718 962 690
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