ANAHEIM, Calif.–(BUSINESS WIRE)–Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced data from the first part of an ongoing Phase 2 study, which showed that treatment with a combination of two cystic fibrosis transmembrane conductance regulator (CFTR) modulators, KALYDECO™ (ivacaftor, VX-770) and VX-809, may improve outcomes for people with the most common form of cystic fibrosis (CF) by targeting the underlying cause of the disease. CF is caused by a defective protein known as CFTR, which is responsible for regulating the flow of chloride across the cell surface in the lungs to help hydrate and clear mucus from the airways. In people with the most common mutation in the CF gene, known as the F508del, the CFTR protein does not reach the cell surface in normal amounts, resulting in a buildup of mucus and other complications that can lead to lung damage. This type of CF is one of the most severe forms of the disease. In the United States, approximately 90 percent of people with CF have at least one copy of the F508del mutation. VX-809, known as a CFTR corrector, is designed to help the CFTR protein reach the cell surface. KALYDECO (kuh-LYE-deh-koh), known as a CFTR potentiator, aims to help the protein function more normally once it reaches the cell surface.

“In people with the most common form of CF, the CFTR protein is defective – it doesn’t usually reach the cell surface and is relatively inactive if it does”

there were three treatment arms in Part 1 of this 21-day study that evaluated VX-809 (200 mg once daily) or placebo alone for 14 days, followed by VX-809 (200 mg) in combination with KALYDECO (150 mg or 250 mg every 12 hours) or placebo for seven days. The study enrolled people 18 and older with two copies of the F508del mutation. Data from the first part of this study showed that there was a nearly two-fold greater reduction in sweat chloride between Day 14 and Day 21 when KALYDECO (250 mg) was added to VX-809 compared to those who continued to receive VX-809 alone. Topline results from Part 1 of this study were announced in June 2011 and complete data are now being presented at the 25th Annual North American CF Conference (NACFC), November 3-5, 2011 in Anaheim, Calif.

“The first part of this study has given us important information about how the combination of a CFTR potentiator and corrector may help people with the most common form of cystic fibrosis, which is also one of the most severe forms of the disease,” said Chris Wright, M.D., Ph.D., Senior Vice President and Head of Global Medicines Development and Affairs for Vertex. “We look forward to evaluating higher doses and longer treatment times in the second part of this study.”

No significant differences were seen between study groups in the frequency or type of adverse events, and no serious adverse events occurred. Respiratory-related adverse events were the most commonly reported, with an overall incidence of 50 percent across treatment arms.

The CFTR protein functions as a chloride channel, enabling the movement of chloride, with secondary effects on sodium ions into and out of these cells. When the protein is defective or absent, as in CF, the salt balance in certain tissues in the body is disturbed. This causes people with CF to have more chloride, or salt, in their sweat. Elevated sweat chloride levels are a diagnostic hallmark that occur in people with CF and result directly from defective CFTR function in the sweat ducts. Measurement of the chloride in sweat has been the standard method for diagnosing CF for more than 40 years.

“In people with the most common form of CF, the CFTR protein is defective – it doesn’t usually reach the cell surface and is relatively inactive if it does,” said Michael Patrick Boyle, M.D., F.C.C.P., Associate Professor, Director of the Johns Hopkins Adult Cystic Fibrosis Center and lead investigator for this study. “The reductions in sweat chloride seen in this study demonstrate that the combination of KALYDECO and VX-809 are working together to repair these defects and that we’re on the right track for potentially helping more people with CF.”

About the Phase 2 Study

these data are from the first part of an ongoing, multiple-part, randomized, double-blind, placebo-controlled Phase 2 trial that will inform future clinical studies of a CFTR corrector, VX-809, in combination with CFTR potentiator, KALYDECO. The first part of the study enrolled 62 people with CF aged 18 years or older who had two copies of the F508del mutation in the CFTR gene. The primary goals of the trial were to evaluate the safety and tolerability and the effect on CFTR function of the combination of VX-809 and KALYDECO as measured by sweat chloride.

Part 2 of this trial will evaluate dosing of VX-809 alone for four weeks followed by dosing of KALYDECO and VX-809 in combination for four weeks. The study is expected to evaluate multiple dose levels of VX-809, including doses higher than those studied in the first part of the trial, and longer dosing periods. The study is expected to enroll approximately 100 people with CF who have one or two copies of the F508del mutation. Similar to Part 1, the primary goals of the second part of the trial are to evaluate safety and tolerability and the effect of the combination of KALYDECO and VX-809 on CFTR function as measured by sweat chloride. Lung function will be measured as a secondary endpoint. Patient screening for Part 2 of this study began in October 2011.

Final Results from Part 1 of the Phase 2 Study

Safety: In Part 1 of this study, no serious adverse events were reported, and the adverse event profile observed during the 7-day portion in which VX-809 and KALYDECO were dosed in combination was similar to the profile observed during the prior 14-day dosing period in which VX-809 was dosed as monotherapy. The most commonly reported adverse events were respiratory in nature and occurred in approximately half of people across all arms of the study. One person receiving VX-809 in the monotherapy portion of the study discontinued treatment due to an increase in respiratory symptoms during the first 7 days of the study.

Sweat Chloride: A co-primary endpoint of the study was the effect on CFTR function as measured by sweat chloride during the combination-dosing portion of the study (Day 14 to Day 21). 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 Part 1 of this study, the baseline sweat chloride levels across the three study arms were approximately 100 mmol/L. The within-group mean change in sweat chloride from baseline for each of the treatment groups was as follows:

Treatment Arm       Within-Group mean Change in Sweat Chloride from Baselines (Day 0 and Day 14)       Day 0 — 14: VX-809 Alone       Day 14 — 21: VX-809 inCombination with KALYDECO Arm 1 (n=20): VX-809 (200mg);VX-809 (200 mg) in combinationwith KALYDECO (150 mg) -4.21 mmol/L (p=0.008)       -2.24 mmol/L (p=0.163) Arm 2 (n=21): VX-809 (200mg);VX-809 (200 mg) in combinationwith KALYDECO (250 mg)             -9.10 mmol/L (p<0.001) Arm 3 (n=21): VX-809 placebo;VX-809 placebo in combinationwith KALYDECO placebo       -2.86 mmol/L (p=0.179)       +1.25 mmol/L (p=0.446)

A statistically significant reduction in sweat chloride of 9.10 mmol/L (p<0.001) was observed after KALYDECO (250 mg) was added to VX-809 (200 mg) from Day 14 to Day 21. as compared to baseline (Day 0), people who received the combination regimen in this arm had a 13.17 mmol/L reduction in sweat chloride.

Eight of the 17 patients with evaluable data in Arm 2 had a reduction of sweat chloride that exceeded 15.0 mmol/L, while four of these 17 patients had a reduction of sweat chloride that exceeded 20.0 mmol/L. four of the 21 patients in this arm were not part of the responder analysis (n=17) because they did not have evaluable data at the relevant time points. across the treatment arms, sweat chloride levels returned to baseline following the completion of dosing with VX-809 and KALYDECO.

About CFTR and CFTR Modulators

CF is caused by defective or missing CF transmembrane conductance regulator (CFTR) proteins, which result in poor ion flow across cell membranes, including in the lungs, causing the accumulation of abnormally thick, sticky mucus that leads to chronic lung infections and progressive lung damage. Approximately 90 percent of people with CF have at least one copy of the F508del mutation. In these people CFTR proteins do not reach the cell surface in normal amounts and don’t function properly at the cell surface. as a CFTR corrector, VX-809 aims to increase CFTR function by increasing the movement of CFTR to the cell surface. once these CFTR proteins are at the cell surface, KALYDECO, a CFTR potentiator, aims to keep them open longer to improve the transport of chloride ions across the cell membrane.

Vertex submitted requests to the U.S. Food and Drug Administration and the European Medicines Agency to use the trade name KALYDECO (ivacaftor) for VX-770.

About Cystic Fibrosis

CF is a 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. According to the 2010 Cystic Fibrosis Foundation Patient Registry Annual Data Report, approximately 4 percent of the total CF patient population in the United States have at least one copy of the G551D mutation, 48 percent of the total CF patient population in the United States have two copies of the F508del mutation and an additional 40 percent of the total CF patient population have one copy of the F508del mutation.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)

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 KALYDECO and other 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 cff.org.

About Vertex

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 Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 1,900 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 including statements regarding (i) the data from the first part of the Phase 2 study supporting the approach of treating the most common form of CF by targeting the underlying cause of the disease with a combination of KALYDECO and VX-809; (ii) the belief that Vertex is on the right track for potentially helping more people with this combination approach and (iii) the design and goals of the second part of the Phase 2 study. While the Company believes the forward-looking statements contained in this press release are accurate, those statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. these risks and uncertainties include, among other things, the risk that efforts to develop VX-809 in combination with KALYDECO may not proceed due to technical, scientific, commercial, financial or other reasons, that an adverse event profile for VX-809 or KALYDECO could be revealed in the future that could put further development of VX-809 or KALYDECO in jeopardy, 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 vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.