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Final Data from Phase 2 Combination Study of VX-809 and KALYDECO™ (ivacaftor) Showed Statistically Significant Improvements in Lung Function in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation
- Mean absolute improvement in lung function of 6.1 percentage points within group (p < 0.001) and 8.6 percentage points compared to placebo (p < 0.001) in homozygous patients receiving combination treatment (Day 28 to 56) with highest study dose of VX-809 (600mg) -
- Adverse events were similar between treatment and placebo groups; most events were mild to moderate -
- Pivotal program to evaluate VX-809 (600mg) in combination with KALYDECO (250mg) planned to start in early 2013, pending discussions with regulatory agencies -
The study also included an exploratory treatment group that looked at a subset of heterozygous patients who have one copy of the F508del mutation and a second mutation that is not expected to respond to KALYDECO dosed as monotherapy. This group of patients received VX-809 (600mg) and KALYDECO on the same dosing schedule as homozygous patients. Heterozygous patients who were treated with the combination experienced a mean absolute improvement in lung function compared to placebo from Day 28 to 56. Based on these data, Vertex plans to conduct additional clinical studies of VX-809 and KALYDECO in heterozygous patients.
"We are focused on developing additional medicines to treat the
underlying cause of cystic fibrosis, and these data represent exciting
progress toward that goal," said
Vertex will host a conference call for investors and media today,
This is a Phase 2 randomized, double-blind, placebo-controlled study.
Data from the first part of this study (Cohort 1) were announced in 2011
and an interim analysis of the second part (Cohort 2) was announced in
LUNG FUNCTION: PATTERN OF RESPONSE
Progressive lung disease is a major source of illness and is the primary cause of death in people with CF. Typically, people with CF lose 1 percent to 2 percent of their lung function (FEV1) each year.
During the first 28 days of the study, there was a decline in lung function in the majority of patients in both the treatment and placebo groups. In contrast, from Day 28 to 56, when the treatment groups received the combination of VX-809 and KALYDECO, there was a mean absolute improvement in lung function in each of the treatment groups, while lung function continued to decline for the placebo group.
HOMOZYGOUS PATIENTS RECEIVING VX-809 -- 600mg
Lung Function: Homozygous patients treated with the highest dose of VX-809 (600mg) in combination with KALYDECO from Day 28 to 56 experienced a mean absolute improvement in lung function of 8.6 percentage points compared to placebo (p < 0.001) and a mean absolute improvement of 6.1 percentage points within group (p < 0.001). Fifty-five percent of these patients experienced an absolute improvement in lung function of 5 percentage points or more compared to 9.5 percent of those treated with placebo. Twenty-five percent experienced an absolute improvement of 10 percentage points or more compared to 0 percent of those treated with placebo.
Mean Absolute Changes in Lung Function (percent predicted FEV1)
Day 0 to 28
|Day 28 to 56|
Placebo within group
|-0.9 (p=0.54)||-2.5 (p=0.08)|
VX-809 alone (600mg; QD) for 28 days followed
|-2.9 (p=0.07)||+6.1 (p < 0.001)|
VX-809 alone (600mg; QD) for 28 days followed
|-2.0 (p=0.36)||+8.6 (p < 0.001)|
|Day 0 to 28||Day 28 to 56|
≥ 5 percentage point
|13.0% (3/23)||10.0% (2/20)||9.5% (2/21)||55.0% (11/20)|
≥ 10 percentage point
|4.3% (1/23)||5.0% (1/20)||0.0% (0/21)||25.0% (5/20)|
From Day 0 to 56, patients receiving VX-809 (600mg) and KALYDECO experienced a mean absolute improvement in lung function of 6.7 percentage points compared to placebo (p=0.002) and a 3.4 percentage point improvement within group (p=0.03). Patients treated with placebo experienced a mean absolute decline in lung function of 3.3 percentage points (p=0.03) over the same time period.
Sweat chloride: Elevated sweat chloride levels are a diagnostic hallmark in CF and are the result of CFTR protein dysfunction. Although not a clinically validated endpoint, a reduction in sweat chloride is considered to be a biomarker of improved CFTR function in the skin.
One of the two primary endpoints in this study was change in sweat chloride from Day 28 to 56 compared to placebo. There was no decrease in sweat chloride among those receiving placebo from Day 0 to 28 or from Day 28 to 56. In homozygous patients treated with 600mg of VX-809 alone for 28 days, there was a statistically significant mean decrease in sweat chloride of 6.4 mmol/L compared to placebo (p=0.01). An additional mean decrease in sweat chloride of 3.7 mmol/L compared to placebo was observed with combination treatment between Day 28 and 56, which was not statistically significant.
HOMOZYGOUS PATIENTS RECEIVING VX-809 -- 400mg, 200mg
Lung function: During the combination treatment period (Day 28 to 56), there were statistically significant mean absolute improvements in lung function compared to placebo in both the 200mg and 400mg VX-809 treatment groups. These improvements were smaller than those seen during the combination treatment period in the VX-809 600mg group.
Sweat chloride: A statistically significant reduction in sweat chloride was observed from Day 0 to 28 in homozygous patients treated with VX-809 (200mg, 400mg) alone compared to placebo. Additional reductions in sweat chloride were observed between Day 28 and 56, but were not statistically significant.
HETEROZYGOUS PATIENTS RECEIVING VX-809 -- 600mg
Lung function: In heterozygous patients who received 600mg of VX-809 in combination with KALYDECO, there was a mean absolute improvement in lung function from Day 28 to 56 compared to placebo. This improvement in lung function was smaller than the improvement seen in homozygous patients receiving 600mg of VX-809 in combination with KALYDECO. Based on these data, Vertex plans to conduct additional clinical studies of VX-809 and KALYDECO in heterozygous patients.
SAFETY DATA FOR ALL PATIENTS
Safety: A co-primary endpoint in this study was safety. The final safety results are consistent with those announced at the time of the interim analysis and include data from all 109 patients enrolled in the study. As previously reported, 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 to moderate in severity and similar between treatment and placebo groups. The rate of serious adverse events was also similar between treatment and placebo groups.
VX-809 and KALYDECO were discovered as part of a collaboration with
Conference Call for Media and Investors
Vertex will host a conference call and webcast today,
To listen to the live call on the telephone, dial 1-877-250-8889 (
The conference ID number for the live call and replay is 95886622.
The call will be available for replay via telephone commencing
Following the live webcast, an archived version will be available on
Vertex's website until
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 30,000 people in
CF is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. 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. 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. Globally, nearly half (46 percent) of people with CF have two copies of the F508del mutation and an additional one-third (33 percent) have one copy of the F508del mutation.
KALYDECO™ (ivacaftor) is the first treatment to target the underlying
cause of CF. KALYDECO (150mg, q12h) was approved by the
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. Serious side effects that may or may not be related to KALYDECO but which occurred more frequently in patients treated with KALYDECO included stomach (abdominal) pain, high liver enzymes in the blood, and low blood sugar. 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 U.S. Prescribing Information for KALYDECO at www.KALYDECO.com.
Collaborative History with
Vertex initiated its CF research program in 1998 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the
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 diseases.
Founded more than 20 years ago in
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, Dr. Wright's statements in the third paragraph of this press
release, Dr. Boyle's statements in the fourth paragraph of this press
release and statements regarding (i) Vertex's plan to start a pivotal
program to evaluate VX-809 (600mg) in combination with KALYDECO (250mg)
in early 2013, pending discussions with regulatory agencies, and (ii)
Vertex's plan to conduct additional clinical studies of VX-809 and
KALYDECO in heterozygous patients. 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 outcomes of future clinical trials of VX-809 and KALYDECO may
be less favorable than the data reported today, or may not be favorable
at all, that the initiation of pivotal clinical trials evaluating VX-809
in combination with KALYDECO may be delayed or prevented as a result of
discussions with regulatory agencies or other factors and the other
risks listed under Risk Factors in Vertex's annual report and quarterly
reports filed with the
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