Vertex Pharmaceuticals Incorporated : Vertex Corrects and Provides Additional Data from Recent Interim Analysis of Phase 2 Combination Study of VX-809 and KALYDECO™ (ivacaftor) in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation
05/29/2012| 07:05am US/Eastern
- Corrected Data: Responder analysis showed 35% of patients
experienced an absolute improvement in lung function (FEV1)
of at least 5 percentage points and 19% had at least a 10
percentage-point improvement when treated with VX-809 and KALYDECO -
- Additional Data: Patients treated with VX-809 and KALYDECO
experienced an 8.5 percentage point mean absolute improvement in lung
function compared to patients treated with placebo (p=0.002) -
- Vertex plans to start a pivotal study of this combination to treat
the underlying cause of CF in adults with two copies of the F508del
mutation, pending final data and discussions with regulatory agencies -
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today a
correction to the previously reported responder analysis, as well as
additional data from, the recent interim analysis of an ongoing Phase 2
study of VX-809 and KALYDECO™ (ivacaftor) that showed significant
improvements in lung function (forced expiratory volume in one second,
FEV1) among adults with cystic fibrosis (CF) who have two
copies (homozygous) of the most common mutation in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene, F508del. As
previously announced, there was a statistically significant improvement
in lung function (absolute change in percent predicted FEV1)
across the combined treatment groups relative to baseline compared to
placebo (p=0.002). Today's announcement provides a correction to the
responder analysis (n=37) for the absolute improvement in lung function
compared to baseline and, for the first time, provides the mean absolute
improvement in lung function compared to placebo observed among patients
who received VX-809 (200mg, 400mg, 600mg; QD) and KALYDECO (250mg;
q12h). The data reported today and earlier this month are based on 37
patients who completed 56 days of treatment with VX-809 and KALYDECO and
11 patients with one or two copies of the F508del mutation who received
placebo. Vertex will host a conference call for investors and media
today, May 29, 2012 at 8:00 a.m. ET, to discuss the correction and
On May 7, 2012, the company announced that approximately 46 percent
(17/37) of patients with two copies of the F508del mutation experienced
an improvement in lung function (FEV1) of 5 percentage points
or more and approximately 30 percent (11/37) experienced an improvement
of 10 percentage points or more from baseline to Day 56 when treated
with the combination of VX-809 and KALYDECO. These results were relative
improvements, not absolute improvements as originally reported.
The actual absolute improvements in lung function for these patients
are: approximately 35 percent (13/37) experienced an absolute
improvement of 5 percentage points or more and approximately 19 percent
(7/37) experienced an absolute improvement of 10 percentage points or
more from baseline to Day 56. As previously announced, none of the
patients treated with placebo (0/11) achieved a 5 percentage-point or
more mean absolute improvement in lung function from baseline to Day 56.
Additional data from the interim analysis are provided today for people
with two copies of the F508del mutation. A mean absolute improvement in
lung function of 8.5 percentage points was observed among those who were
treated with VX-809 and KALYDECO compared to placebo (p=0.002). In
addition, the within-group mean absolute improvement from baseline to
Day 56 was 4.0 percentage points (p=0.002) for patients treated with the
combination. From baseline to Day 56, those treated with placebo
experienced a mean absolute decrease in lung function of 4.6 percentage
These data are from a planned interim analysis that was conducted after
approximately half of the patients completed 56 days of treatment.
Evaluation of patients with one copy (heterozygous, n=21) of the F508del
mutation is ongoing. All patients have now completed dosing. Analyses
are ongoing and complete data, including statistical analyses for all
patient groups, will be available mid-year. Vertex plans to start a
pivotal study of VX-809 and KALYDECO in people with two copies of the
F508del mutation, pending final study results and discussions with
Interim Lung Function Data
VX-809 alone (200mg, 400mg or 600mg; QD) for 28 days
followed by the addition of KALYDECO (250mg, q12h) for 28
Mean absolute change in FEV1 from baseline to Day 56
compared to placebo
Mean absolute change in FEV1 from baseline to Day 56 for
pooled treatment and placebo groups
? 5 percentage point absolute improvement from baseline to Day 56
35% (13/37) *
? 10 percentage point absolute improvement from baseline to Day 56
19% (7/37) *
* On May 7, 2012, Vertex announced that approximately 46 percent
(17/37) experienced an improvement from baseline to Day 56 in lung
function of 5 percentage points or more, and approximately 30
percent (11/37) experienced an improvement from baseline to Day 56
of 10 percentage points or more. These results were relative
improvements, not absolute improvements as originally reported.
"The improvements in lung function seen to date in this study exceeded
our expectations. We're continuing to move forward as quickly as
possible toward a pivotal study of VX-809 and KALYDECO in people with
two copies of the F508del mutation," said Chris Wright, M.D., Ph.D.,
Vertex's Senior Vice President, Global Medicines Development and Medical
Safety results are the same as those announced on May 7, 2012 and
include data from all patients who had started treatment prior to this
interim analysis. VX-809 was generally well tolerated alone and in
combination with KALYDECO. The most common adverse events were pulmonary
in nature. Most adverse events were mild or moderate in severity and
comparable between treatment and placebo groups. The rate of serious
adverse events was similar between treatment and placebo groups.
About this Phase 2 Study
Data from the first part of this study were announced in 2011. The
interim data announced this month are from the second part of the
ongoing Phase 2 randomized, double-blind, placebo-controlled study. This
part of the study enrolled 108 people with CF ages 18 and older with one
or two copies of the F508del mutation who were divided into five
treatment groups of approximately 20 patients each. Three groups of
homozygous patients were randomized to receive VX-809 alone (200mg,
400mg or 600mg) for 28 days and then in combination with KALYDECO
(250mg) for an additional 28 days. One group of heterozygous patients
received VX-809 alone (600mg) for 28 days and then in combination with
KALYDECO (250mg) for an additional 28 days. The improvements in lung
function were primarily observed following the addition of KALYDECO from
Day 28 and maintained through Day 56. The placebo group includes both
homozygous and heterozygous patients.
Cystic fibrosis is caused by defective or missing CFTR proteins
resulting from mutations in the CFTR gene. Located at the surface
of cells, CFTR proteins act as channels to regulate the flow of salt and
water into and out of the cells. In people with the F508del mutation in
the CFTR gene, little to no CFTR protein reaches the cell
surface. As a result, thick, sticky mucus builds up and blocks the
passages in many organs, leading to a variety of symptoms. In
particular, mucus builds up and clogs the airways in the lungs, causing
chronic lung infections and progressive lung damage. VX-809, known as a
CFTR corrector, is believed to help CFTR proteins reach the cell
surface. KALYDECO, known as a CFTR potentiator, keeps the CFTR protein
channels open longer to increase the flow of salt and water into and out
of the cell.
VX-809 and KALYDECO were discovered as part of a collaboration with
Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug
discovery and development affiliate of the Cystic Fibrosis Foundation.
Conference Call for Media and Investors
Vertex will host a conference call and webcast today, May 29, 2012 at
8:00 a.m. ET to discuss this interim data analysis. The conference call
will be webcast live and a link to the webcast may be accessed from the
'Events & Presentations' page of the Vertex website at www.vrtx.com.
To listen to the live call on the telephone, dial 1-866-516-1003 (United
States and Canada) or 1-973-200-3090 (International). To ensure a timely
connection, it is recommended that users register at least 15 minutes
prior to the scheduled webcast.
The conference ID number for the live call and replay is 86428080.
The call will be available for replay via telephone commencing May 29,
2012 at 12:00 p.m. ET running through 5:00 p.m. ET on June 5, 2012. The
replay phone number for the United States and Canada is 1-855-859-2056.
The international replay number is 1-404-537-3406.
Following the live webcast, an archived version will be available on
Vertex's website until 5:00 p.m. ET on June 12, 2012. Vertex is also
providing a podcast MP3 file available for download on the Vertex
website at www.vrtx.com.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 30,000 people in the United States and 70,000 people
worldwide. Today, the median predicted age of survival for a person with
CF is approximately 38 years but the median age of death remains in the
mid-20s. There are more than 1,800 known mutations in the CFTR
gene. Some of these mutations, which can be determined by a genetic, or
genotyping test, lead to CF by creating non-working or too few CFTR
proteins at the cell surface. The absence of working CFTR proteins
results in poor flow of salt and water into and out of the cell in a
number of organs, including the lungs.
In people with the most common mutation in the CFTR gene,
F508del, little to no CFTR protein reaches the cell surface. Globally,
nearly half (46 percent) of people with CF have two copies of the
F508del mutation and one-third (33 percent) have one copy of the F508del
KALYDECO™ (ivacaftor) is the first treatment to target the underlying
cause of CF. KALYDECO (150mg, q12h) was approved by the U.S. Food and
Drug Administration (FDA) in January 2012 for use in people with CF ages
6 and older who have at least one copy of the G551D mutation in the CFTR
gene. On May 25, 2012, Vertex received a positive European CHMP opinion
Vertex retains worldwide rights to develop and commercialize KALYDECO.
Indication and Important Safety Information
KALYDECO (150mg, q12h) is a prescription medicine used for the treatment
of cystic fibrosis (CF) in patients age 6 years and older who have a
certain mutation in their CFTR gene called the G551D mutation.
KALYDECO is not for use in people with CF due to other mutations in the CFTR
gene. It is not effective in CF patients with two copies of the F508del
mutation (F508del/F508del) in the CFTR gene.
It is not known if KALYDECO is safe and effective in children under 6
years of age.
KALYDECO should not be used with certain medicines, including the
antibiotics rifampin and rifabutin; seizure medications (phenobarbital,
carbamazepine, or phenytoin); and the herbal supplement St. John's Wort.
KALYDECO can cause serious side effects. High liver enzymes in the blood
have occurred in patients taking KALYDECO as well as those receiving
placebo. Regular assessment is recommended.
The most common side effects associated with KALYDECO include headache;
upper respiratory tract infection (common cold) including 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. Patients should
tell their healthcare providers about any side effect that bothers them
or doesn't go away.
Please see full Prescribing Information for KALYDECO at www.KALYDECO.com.
Collaborative History with Cystic Fibrosis Foundation Therapeutics,
Vertex initiated its CF research program in 1998 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. This collaboration was
expanded to support the accelerated discovery and development of
Vertex's CFTR modulators.
About the Cystic Fibrosis Foundation
The Cystic Fibrosis Foundation is the world's leader in the search for a
cure for cystic fibrosis. The Foundation funds more CF research than any
other organization and nearly every CF drug available today was made
possible because of Foundation support. Based in Bethesda, Md., the
Foundation also supports and accredits a national care center network
that has been recognized by the National Institutes of Health as a model
of care for a chronic disease. The CF Foundation is a donor-supported
nonprofit organization. For more information, visit www.cff.org.
Vertex creates new possibilities in medicine. Our team discovers,
develops and commercializes innovative therapies so people with serious
diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to
cure or significantly advance the treatment of hepatitis C, cystic
fibrosis, rheumatoid arthritis, epilepsy and other life-threatening
Founded more than 20 years ago in Cambridge, MA, we now have ongoing
worldwide research programs and sites in the U.S., U.K. and Canada.
Today, Vertex has more than 2,000 employees around the world, and Science
magazine named Vertex number one on its 2011 list of Top Employers in
the life sciences.
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 Dr. Wright's
statements in the sixth paragraph of this press release, and statements
regarding (i) Vertex's plan to start a pivotal study of VX-809 and
KALYDECO in people with two copies of the F508del mutation, pending
final data and discussions with regulatory agencies, (ii) the expected
availability of complete data from the study in mid-2012 and (iii) the
evaluation of patients with one copy of the F508del mutation being
ongoing. While Vertex believes the forward-looking statements contained
in this press release are accurate, 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 the final outcomes of
this clinical trial or future clinical trials of VX-809 and KALYDECO may
be less favorable than the interim analysis reported today, or may not
be favorable at all, that final data from heterozygous patients may not
be favorable or may be less favorable than the data from homozygous
patients, that final data and/or discussions with regulatory agencies
regarding the scope and design of future clinical trials may result in
additional clinical trials needing to be conducted before Vertex can
initiate the first pivotal clinical trials evaluating VX-809 in
combination with KALYDECO 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.
Vertex Pharmaceuticals Incorporated
© Business Wire 2012