Clinical Researchers Present Promising Results for VX-770


Company News Release

Clinical Researchers Present Promising Results for VX-770, an Oral Investigational Agent that Targets a Defective Protein Responsible for Cystic Fibrosis.

At the 31st European Cystic Fibrosis Society (ECFS) Annual Meeting in Prague, Czech Republic, researchers will today present interim results from the first clinical trial of the investigational oral agent VX-770 in cystic fibrosis patients. Data from the interim analysis suggested that dosing of VX-770, an investigational CF potentiator, as an oral agent for 14 days resulted in improved lung function and in an improved function of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein as measured by changes in sweat chloride levels and changes in nasal potential difference (NPD). The data will be presented in an oral session at the ECFS on Friday, June 13 at 5:30 p.m. CEST p.m. by Frank Accurso, M.D., Director of the Cystic Fibrosis Center and Professor of Pediatrics at the University of Colorado School of Medicine, USA.

"While these are early data, it is unprecedented for an investigational oral compound for the treatment of CF to have such a marked effect on multiple measures of CF disease activity. We saw an average improvement in lung function of 10 percent in patients receiving the highest dose, compared to no observed improvement in patients who received placebo," said Dr. Accurso. "These data suggest that VX-770 may be able to improve lung function by targeting an underlying defect in CFTR that causes the disease. In patients with CF, inadequately functioning or missing CFTR is believed to result in abnormal balance of fluid and salt in the airways. These are early clinical data in a subset of patients with malfunctioning CFTR, but an important proof-of-concept, and we look forward to evaluating the longer-term safety and efficacy of VX-770 in additional studies."

Interim Analysis Summary:

The results, which were first reported earlier this year and are being presented in a medical meeting for the first time today, are from 20 patients with the G551D mutation in CFTR who received either VX-770 or placebo in addition to standard therapies for 14 days as part of a blinded, randomized, two-period crossover study design. Four subjects received placebo during both 14-day dosing periods; 8 subjects received 25 mg of VX-770 twice-daily during one period and 75 mg in the other; and 8 subjects received 75 mg of VX-770 twice-daily during one period and 150 mg, the highest dose in the study, during the other dosing period. There was a one to four week wash-out between each dosing period.

-- Safety: In the 14-day trial, VX-770 appeared to be well-tolerated. Observed adverse events were similar between VX-770 and placebo treatment. Two serious adverse events were observed in one patient and were not attributed to VX-770.

-- Lung Function: In the Phase 2a trial, lung function in patients was assessed with FEV(1), a standard test that measures the amount of air that can be exhaled in one second. FEV(1) is the lung function test most commonly used to monitor progression of airway disease in CF patients. Patients with CF typically experience a decline in lung function of 1-2% per year during their life, as measured by FEV(1). Over the 14-day dosing period in the Phase 2a study, patients receiving the highest dose of VX-770 (150mg twice daily) showed a mean increase from baseline in FEV(1) of 10.1%, or 0.22L (p less than 0.008). In contrast, patients receiving placebo showed a slight decrease in FEV(1) (less than 1%; 0.03L) over the 14-day period.

-- Sweat Chloride: Elevated sweat chloride levels are a diagnostic hallmark that occur in all CF patients 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 skin test. Patients with CF typically have sweat chloride levels in excess of 60 mmol/L, while normal values are less than 40 mmol/L. In patients receiving the highest dose of VX-770 (150mg twice daily) in the Phase 2a study, sweat chloride decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L over the 14-day dosing period (p less than 0.0001). Six of 8 patients in the 150 mg dose group achieved a decrease in sweat chloride to below 60 mmol/L. There was no notable change in sweat chloride in patients receiving placebo.

-- Nasal Potential Difference (NPD): NPD assesses several aspects of ion channel activity by measuring voltage changes across the nasal epithelia and is used as a direct measure of CFTR activity and chloride ion movement in upper airway epithelial cells. Typical assessments of CF patients using NPD show very low chloride ion secretion in the nasal passage. After 14 days of dosing, patients receiving the highest dose of VX-770 (150 mg twice daily) showed a significant mean change from baseline in chloride ion secretion in NPD of -5.4 mV (p=.01). In contrast, in those treated with placebo, a mean change of -1.74 mV was observed.

Robert J. Beall, Ph.D., President and Chief Executive Officer of the Cystic Fibrosis Foundation, said, "More than 10 years ago, the Cystic Fibrosis Foundation believed that Vertex's approach to treating CF by directly targeting CFTR function - the underlying mechanism of the disease - was an important opportunity to meaningfully change the course of cystic fibrosis. We are highly encouraged by the early clinical data for VX-770, as these results represent a significant step forward in understanding the potential for new treatment approaches for the more than 70,000 cystic fibrosis patients worldwide."

About the Phase 2a Clinical Trial:

Results reported today are from an interim analysis of Part 1 of an ongoing Phase 2a clinical trial evaluating the safety and pharmacokinetics of VX-770, and investigating the effect of VX-770 on clinical measures of lung function and CFTR activity in patients 18 years of age or older who possess the G551D mutation. In Part 1 of the trial, 20 patients with the G551D mutation in CFTR received either VX-770 or placebo in addition to standard therapies for 14 days as part of the trial's blinded, randomized, crossover design. Based on the interim results, Vertex expects to proceed to Part 2 of the trial, which will enroll approximately 18 patients for dosing of VX-770 or placebo for 28 days. In the trial, VX-770 is being dosed as an oral therapy.

About CF and VX-770:

Cystic Fibrosis affects approximately 70,000 people worldwide. Cystic fibrosis is caused by a genetic mutation that results in a malfunctioning or missing CFTR protein on cell surfaces, that results in an imbalance of salt and water. This fluid imbalance in the lungs causes a cascade of mucus plugging, infection and inflammation that characterizes CF, and accounts for a large portion of the morbidity and mortality seen with CF. Current therapies treat CF by managing the symptoms caused by the salt/water imbalance. While aggressive management of CF has improved long-term outcomes in CF patients, the median predicted life expectancy is currently 37 years.

VX-770, an investigational oral potentiator, is intended to help restore the balance of salt and water by acting directly on the malfunctioning CFTR protein. Clinical development of VX-770 is currently focused on a subset of CF patients who have a specific type of CFTR mutation known as G551D that constitutes approximately 4 percent of the CF patient population in the U.S. Vertex also plans to evaluate VX-770 in patients with other mutations that result in malfunctioning CFTR on the cell surface. VX-770 was advanced into preclinical development based on successful collaborative research with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT) that incorporated capabilities and proprietary ion channel research from Vertex's San Diego research site.

About Vertex:

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, inflammation, autoimmune diseases, cancer, pain and cystic fibrosis. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

Vertex Safe Harbor Statement:

This press release may contain forward-looking statements, including statements that (i) results from this interim analysis support the hypothesis that improving chloride ion transport in CF patients may correlate to improvements in lung function and provide patient benefit; (iii) VX-770 may be able to improve lung function by targeting an underlying defect in CFTR that is a cause of CF; (iv) Vertex expects to move into the second part of its Phase 2 trial of VX-770; (v) Vertex plans to evaluate VX-770 in patients with other mutations that result in malfunctioning CFTR on the cell surface. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause Vertex's actual results to vary materially. These risks and uncertainties include, among other things, the risks that efforts to develop VX-770 may not proceed due to financial, technical, scientific, commercial or other reasons, that clinical trials may not proceed as planned due to technical, scientific, supply or patient enrollment issues, that additional clinical studies of VX-770 will not reflect the results obtained in the study to date and will not support additional development activity, that regulatory authorities will require additional data before engaging in development planning discussions with Vertex, and other risks listed under Risk Factors in Vertex's Form 10-K filed with the Securities and Exchange Commission.

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