Vertex Pharmaceuticals Incorporated today announced positive results from the Phase 3 STRIVE study of VX-770, an oral medicine in development that targets the defective protein that causes cystic fibrosis (CF).

STRIVE was designed to evaluate people with a mutation in the CF gene known as G551D. In this study, profound improvements in lung function (forced expiratory volume in one second, or FEV1) were observed through week 24, and sustained through week 48, among those who received VX-770 (n=83) compared to those treated with placebo (n=78). Significant improvements in all key secondary endpoints were also observed through week 48 among those who received VX-770.

Data from the study showed a mean absolute improvement in lung function from baseline compared to placebo through week 24 of 10.6 percent among those treated with VX-770 (p<0.0001). Mean absolute improvement in lung function among those treated with VX-770 was 10.5 percent through week 48 (p<0.0001).

The primary endpoint of the study was mean absolute change from baseline compared to placebo in percent predicted FEV1 (lung function) through week 24. Data from the study showed a mean absolute improvement in lung function from baseline compared to placebo through week 24 of 10.6 percent among those treated with VX-770. Mean absolute improvement in lung function among those treated with VX-770 was 10.5 percent through week 48.

Highly statistically significant improvements in key secondary endpoints in this study were also reported through week 48. Compared to those treated with placebo, people who received VX-770 were 55 percent less likely to experience a pulmonary exacerbation (periods of worsening in signs and symptoms of the disease requiring treatment with antibiotics) and, on average, gained nearly seven pounds (3.1 kilograms) through 48 weeks. There was a significant reduction in the amount of salt in the sweat (sweat chloride) among people treated with VX-770 in this study. Increased sweat chloride is a diagnostic hallmark of CF. Sweat chloride is a marker of CFTR protein dysfunction, which is the underlying molecular mechanism responsible for CF. People who received VX-770 also reported having fewer respiratory symptoms.

Adverse events that were 5 percent greater among those treated with VX-770 compared to placebo were headache, upper respiratory tract infections, nasal congestion, rash, dizziness and bacteria in the sputum. The most commonly reported serious adverse events included pulmonary exacerbation (13 percent in the VX-770 group compared to 33 percent in the placebo group) and hemoptysis (or bloody cough; 1 percent in the VX-770 group and 5 percent in the placebo group). Discontinuations through 48 weeks due to adverse events were less frequent in the VX-770 treatment group compared to placebo (1 percent compared to 5 percent).

"Treating the underlying cause of cystic fibrosis with VX-770 led to clinical improvements that were far beyond our expectations, providing support for an entirely new approach to the treatment of this disease," said Peter Mueller, Ph.D., Executive Vice President, Global Research and Development, and Chief Scientific Officer for Vertex. "All primary and key secondary outcome measures in this study supported VX-770 over placebo. Patients' lung function improved, they gained weight, experienced fewer respiratory symptoms and felt substantially better. Due to the significance of these data and the great need for new, more effective medicines, we will work with regulatory agencies to determine the fastest way to get VX-770 approved for people with this specific type of CF."

"The results from STRIVE are highly encouraging for the CF community and provide scientific evidence supporting our long-standing belief that targeting the underlying defect of CF may have a profound effect on the disease," said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. "We have much more to do to eliminate this disease, but these data are extremely exciting, especially for people with the G551D mutation and their families. They also offer significant hope that a similar approach to treatment may help others living with CF."

All patients who completed 48 weeks of treatment in STRIVE (n=144), including those in the placebo group, were eligible to receive VX-770 as part of an extension study called PERSIST. All patients (n=77) who completed dosing in the VX-770 arm and all but one patient (n=67) in the placebo arm chose to enroll in the extension study and receive VX-770 for up to an additional 96 weeks or until VX-770 is approved.

STRIVE is one of three studies in the VX-770 registration program. Vertex plans to submit data from STRIVE for presentation at an upcoming medical meeting. The registration program for VX-770 also includes two other studies, the Phase 2 DISCOVER study and Phase 3 ENVISION study. Data from DISCOVER were also reported today. Data from ENVISION are expected in mid-2011. Vertex plans to submit regulatory applications for approval in the United States and Europe in the second half of 2011.

Vertex's medicines in development for CF were discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT) to discover and develop novel CFTR modulators. CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Vertex retains worldwide rights to develop and commercialize these potential medicines.

Summary of Key Data from STRIVE

In the STRIVE study, 161 people were enrolled and received at least one dose of either VX-770 as a single 150 mg tablet or placebo twice daily. The study was designed to evaluate VX-770 in people with at least one copy of the G551D CFTR mutation. The primary endpoint of the study was mean absolute change from baseline in predicted FEV1 (lung function) through week 24. Lung function was assessed using a standard test that measures the amount of air a person can exhale in one second (forced expiratory volume in one second, or FEV1).

Preliminary Efficacy Results

Lung Function: Absolute and relative changes in lung function are being reported in today's announcement. The primary endpoint of STRIVE was mean absolute improvement from baseline. Phase 3 results and product labeling for currently available CF medicines generally describe relative improvements in lung function.

Baseline lung function in STRIVE was 63.5 percent predicted for patients in the VX-770 treatment group and 63.7 percent predicted among those in the placebo control group. Results of the STRIVE study showed that people treated with VX-770 achieved a mean absolute improvement from baseline compared to placebo of 10.6 percent through 24 weeks (p<0.0001). Mean absolute improvement in lung function achieved by people who received VX-770 was sustained through 48 weeks (10.5 percent; p<0.0001).

In addition, people treated with VX-770 experienced a 16.7 percent relative mean improvement in lung function from baseline compared to placebo (p<0.0001) through week 24, which was sustained through week 48 (16.9 percent; p<0.0001).

Additional secondary endpoints were measured to observe the effect of VX-770 through week 48. These secondary endpoints included:

Pulmonary Exacerbations: People treated with VX-770 in STRIVE were 55 percent less likely to experience a pulmonary exacerbation compared to those treated with placebo through week 48. Through 48 weeks, 67 percent of people treated with VX-770 were exacerbation free compared to 41 percent of people treated with placebo.

Weight: Many people with CF have a hard time gaining and maintaining weight due to factors such as nutrition, chronic infection and inflammation. In the STRIVE study, those who received VX-770 experienced an average weight gain of approximately 6.8 lbs (3.1 kilograms) at 48 weeks compared to baseline. Those in the placebo group gained approximately 0.9 lbs (0.4 kilograms).

Sweat Chloride: Elevated sweat chloride levels are a diagnostic hallmark that occur in all people with CF and result directly from defective CFTR activity in epithelial cells in the sweat duct. 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. Reduction in sweat chloride is considered to be a marker of improved CFTR function.

In STRIVE, the baseline sweat chloride level for both treatment groups was approximately 100 mmol/L. Statistically significant decreases in measurements of sweat chloride were observed among those treated with VX-770 but not those treated with placebo. Through week 48, mean sweat chloride levels for patients treated with VX-770 were below 60 mmol/L.

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 VX-770 on overall health, daily life, perceived well-being and symptoms. One aspect of the CFQ-R, referred to as the respiratory domain, addresses patient reported symptoms including things such as coughing, congestion, wheezing and other respiratory symptoms. In this study, statistically significant and clinically meaningful improvements in respiratory symptoms (a secondary endpoint of the study) were reported among patients who received VX-770.

DISCOVER Data

Vertex also announced today the results of the Phase 2 DISCOVER study, which was primarily designed to provide additional safety data for VX-770 and is part of the registration program. DISCOVER enrolled 140 people who had two copies of the F508del mutation, which prevents the CFTR protein from moving to its proper location at the cell surface. The majority of people with CF have at least one copy of the F508del mutation.

The primary endpoints of DISCOVER were safety and absolute change from baseline in lung function through 16 weeks. Adverse events were similar between the treatment groups. Adverse events that occurred more frequently (≥5 percent) in the VX-770 treatment group compared to placebo were cough, nausea, rash and contact dermatitis. None of these events were serious or led to discontinuation of VX-770. Data from the DISCOVER study will be submitted for presentation at an upcoming medical meeting.

Mean baseline lung function (FEV1) was 79.7 percent predicted for people who received VX-770 compared to 74.8 percent predicted for patients in the placebo group. Results of the DISCOVER study showed that people treated with VX-770 achieved a mean absolute improvement from baseline compared to placebo of 1.6 percent through 16 weeks (p=0.25). The improvement was not statistically significant and was not considered clinically meaningful. Data from the study also showed a mean relative improvement in lung function from baseline compared to placebo of 2 percent through week 16. A mean reduction in sweat chloride of 2.9 mmol/L compared to placebo through 16 weeks was observed among those treated with VX-770. This improvement was statistically significant but small (p<0.04).

"Based on the results of DISCOVER, we continue to believe the combination of a potentiator and corrector may be the best approach to treating people with two copies of the F508del mutation," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "Data are anticipated later this year from the first study to evaluate the combination of VX-770 and VX-809 in this group of people with cystic fibrosis."

ENVISION Study

In addition to the STRIVE and DISCOVER studies, a third study known as ENVISION is evaluating VX-770 in children 6 to 11 years old with CF who have at least one copy of the G551D mutation. Data from the ENVISION study are anticipated in mid-2011.

Combination Study of VX-770 and VX-809

Vertex is conducting a Phase 2a clinical trial to evaluate multiple combination regimens of VX-770 and VX-809 in people with two copies of the F508del mutation. The first part of the study is designed to evaluate VX-809 (200 mg), or placebo dosed alone for 14 days and in combination with VX-770 (150 mg or 250 mg), or placebo, for seven days. Vertex expects to obtain data from Part One of the trial in the first half of 2011.

Vertex Pharmaceuticals Inc. announced positive results from the Phase 3 STRIVE study of VX-770, a potential therapy that targets the defective protein that causes CF.

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