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Phase 3 Study of KALYDECO™ (ivacaftor) in Children Ages 6 to 11 with a Specific Type of Cystic Fibrosis Showed Significant Improvements in Lung Function and Other Measures of Disease Sustained Through 48 Weeks
- Additional presentations at the
Results from ENVISION showed that children who received KALYDECO (kuh-LYE-deh-koh) experienced rapid and sustained improvements in lung function (forced expiratory volume in one second, FEV1) and other key measures of disease, including weight gain and a reduction in sweat chloride, throughout the 48-week study compared to those treated with a placebo. Patients in the study who received KALYDECO experienced a mean absolute improvement from baseline in lung function of 12.5 percentage points through week 24 (primary study endpoint) and a mean relative improvement from baseline in lung function of 17.4 percent compared to placebo. Through 48 weeks, the mean absolute improvement in lung function for children treated with KALYDECO was 10 percentage points compared to placebo and the relative mean improvement was 15.1 percent from baseline compared to placebo. Phase 3 results and product labeling for currently available CF medicines generally describe relative improvements in lung function. The most commonly reported adverse events were respiratory in nature and comparable across treatment groups.
"The longer people live with CF, the greater the risk of damage and
complications from the disease," said
"The rapid, significant and sustained response to treatment with
KALYDECO offers hope of improved outcomes for people with CF who have
the G551D mutation," said
Adverse events that were more common (≥5 percent) among those treated with KALYDECO compared to placebo were throat pain, headache, upper respiratory tract infections, ear infections, diarrhea and an increase in eosinophil count. Adverse events that were more common among children in the placebo group were cough, vomiting, productive cough, rales (noisy breathing) and a decrease in pulmonary function. Pulmonary exacerbations were uncommon in ENVISION regardless of treatment arm. There were no discontinuations due to adverse events in the KALYDECO treatment group and one discontinuation in the placebo group through 48 weeks.
ENVISION was designed to evaluate KALYDECO in children between the ages of 6 and 11 with at least one copy of the G551D CFTR mutation. In the ENVISION study 52 children were enrolled and received either KALYDECO (n=26) or placebo (n=26) as a single 150 mg tablet every 12 hours. The primary endpoint of the study was mean absolute change from baseline in lung function (FEV1) through week 24. Lung function was assessed using a standard test that measures the amount of air a person can exhale in one second (FEV1).
Lung Function: Baseline lung function in ENVISION was 84.7 percent predicted for children in the KALYDECO treatment group and 83.7 percent predicted among those in the placebo group. Results of the ENVISION study showed that people treated with KALYDECO experienced rapid, significant and sustained improvements in lung function throughout the 48 week study.
Additional secondary endpoints were measured to observe the effects of KALYDECO through week 48. These secondary endpoints included:
Weight: Many people with CF have a hard time gaining and maintaining weight due to factors such as reduced pulmonary function, nutrition, chronic infection and inflammation. In the ENVISION study, children who received KALYDECO gained weight throughout the study. Through week 24, those in the KALYDECO treatment group gained, on average, 3.7kg (8.1 lbs) compared to baseline. Through week 48 the treatment group gained, on average, a total of 5.9 kg (13 lbs) compared to baseline. This was compared to an average gain of 1.8kg (3.9 lbs) among those treated with placebo through week 24 and 3.1kg (6.8 lbs) through week 48 compared to baseline.
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 marker of improved CFTR function. The amount of chloride in the sweat is measured using a standard test. People with CF typically have elevated sweat chloride levels in excess of 60 mmol/L, while normal values are less than 40 mmol/L.
In ENVISION, the baseline sweat chloride level for both treatment groups
was approximately 104 mmol/
Patient-Reported Outcomes: The Cystic Fibrosis Questionnaire — Revised (CFQ-R) is a validated patient-reported outcome tool that was used in this study to measure the impact of KALYDECO on overall health, daily life, perceived well-being and symptoms. A ≥ 4 point change from baseline in the respiratory domain of the CFQ-R is considered clinically meaningful.
One aspect of the CFQ-R, referred to as the respiratory domain, addresses patient reported symptoms. In the ENVISION study, children responded to the CFQ-R and reported a trend toward improvement in respiratory symptoms, which was a key secondary endpoint of the study. Through 48 weeks, there was a 5.1-point difference in responses between the treatment groups. Children treated with KALYDECO reported a 6.1-point change from baseline compared to a 1.0-point change from baseline among those in the placebo group.
12-Week Data from the PERSIST Extension Study
Data from the first 12 weeks of the PERSIST extension study are also being presented at NACFC. PERSIST is a Phase 3, open-label, 96-week, rollover extension trial designed to evaluate the long-term safety and durability of treatment with KALYDECO. This ongoing study enrolled people with at least one copy of the G551D mutation who completed 48 weeks of treatment in the Phase 3 ENVISION and STRIVE studies (placebo and KALYDECO treatment groups) and met other eligibility criteria.
The analysis presented at the meeting includes data from 144 adolescents and adults who completed treatment in the STRIVE study. Seventy-seven of these patients were treated with KALYDECO and 67 received placebo during STRIVE. Through week 48 of the STRIVE study, the mean absolute improvement in lung function for those treated with KALYDECO was 10.5 percentage points compared to placebo (secondary study endpoint) and the relative mean improvement was 16.7 percent from baseline compared to placebo. These absolute and relative changes in lung function among people treated with KALYDECO were sustained through week 12 of the PERSIST rollover study for a total of 60 weeks of treatment.
In addition, data from PERSIST showed that when people treated with a placebo during the STRIVE study rolled over to PERSIST and began receiving KALYDECO, the improvements in lung function through week 12 were similar to those observed among people treated with KALYDECO in the first 12 weeks of STRIVE.
Efficacy Results From the First 12 Weeks of PERSIST for People Who Completed 48 Weeks of Treatment in the Phase 3 STRIVE Study
|Weeks on||Total Weeks on||Absolute Change in||Relative Change in|
|PERSIST||KALYDECO||FEV(1) % Predicted||FEV(1) % Predicted|
|from Baseline**||from Baseline|
Treated with KALYDECO prior to entering PERSIST
Treated with a placebo prior to entering PERSIST
** Baseline defined as FEV1 at time of starting KALYDECO.
The most common adverse events (reported in ≥5 percent of participants overall) were pulmonary exacerbations, cough, productive cough, upper respiratory tract infection, hemoptysis (bloody cough), headache, and abdominal pain. Adverse events were similar to those observed in the STRIVE study.
KALYDECO (ivacaftor, VX-770) is Vertex's lead medicine in development
for the treatment of people with cystic fibrosis and the G551D CFTR
mutation. Known as a CFTR potentiator, KALYDECO is an oral medicine that
aims to help CFTR protein function more normally once it reaches the
cell surface, to help hydrate and clear mucus from the airways. Vertex
retains worldwide rights to develop and commercialize KALYDECO. The
brand name KALYDECO has been approved by the EMA and provisionally
approved by the
Expanded Access Programs for KALYDECO
An expanded access program for KALYDECO is currently open at
participating clinical trial sites in
Vertex is working toward implementing additional expanded access programs in other countries, with a goal of opening programs for eligible patients by the end of 2011.
For more information, please call Vertex Medical Information at 1-877-634-VRTX (8789).
About Cystic Fibrosis
CF is a life-threatening genetic disease affecting approximately 30,000
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 statements
regarding (i) Vertex moving quickly to evaluate other targeted
approaches to CFTR modulation for people with the most common form of
CF; (ii) the potential that KALYDECO will be approved; and (iii) the
possibility that additional expanded access programs will be implemented
with the goal of opening programs to eligible patients by the end of
2011. While the company 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 Vertex could experience
unforeseen delays in obtaining approval to market KALYDECO; that future
outcomes from clinical trials of KALYDECO may not be favorable; that
future scientific, clinical, competitive or other market factors may
adversely affect the potential for KALYDECO and the other risks listed
under Risk Factors in Vertex's annual report and quarterly reports filed
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