Press Release

- Additional presentations at the North American CF Conference include data from PERSIST that showed sustained safety and efficacy of KALYDECO through 60 weeks of treatment among adolescents and adults treated in the Phase 3 STRIVE study -

ANAHEIM, Calif.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced final results from the ENVISION study, the second of two pivotal Phase 3 studies of KALYDECO™ (ivacaftor, VX-770), a medicine in development that targets the defective protein that causes cystic fibrosis (CF). ENVISION (n=52) was designed to evaluate children with CF ages 6 to 11 years who had at least one copy of the G551D mutation. Approximately 1,200 people in the United States and 1,000 people in Europe with CF are estimated to have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. These results, as well as the first data from PERSIST, the long-term follow-up study of adolescents and adults treated in the Phase 3 STRIVE study, are being presented at the 25th Annual North American CF Conference (NACFC), November 3-5, 2011 in Anaheim, Calif.

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 Richard Ahrens, M.D., Co-Director, Cystic Fibrosis Center University of Iowa Children's Hospital and lead investigator of the ENVISION study. "Given this progressive nature of CF, the earlier we can treat patients, the better. These data are encouraging because they confirmed the improvements in lung function, weight gain and sweat chloride reduction we saw among adults who were treated with KALYDECO in the STRIVE study."

"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 Chris Wright, M.D., Ph.D., Senior Vice President and Head of Global Medicines Development and Affairs for Vertex. "We're moving quickly to evaluate other targeted approaches to CFTR modulation for people with the most common form of CF."

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.

Summary of Key Data from ENVISION

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/L. By week two of the study, children treated with KALYDECO experienced an average reduction in sweat chloride of approximately 53 mmol/L. Through week 48, children treated with KALYDECO experienced a reduction of 56 mmol/L, while children treated with placebo experienced an average reduction in sweat chloride of approximately 3 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 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 (n=77)		12		60		11.6		19.4
Treated with a placebo prior to entering PERSIST (n=67)		12		12		10.9		19.9

** 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.

In October 2011, Vertex submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a marketing authorization application (MAA) to the European Medicines Agency (EMA) for KALYDECO, Vertex's CFTR protein potentiator. Vertex requested Priority Review from the FDA and has received agreement from the EMA for accelerated assessment of KALYDECO in Europe.

About KALYDECO

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 FDA for use in connection with KALYDECO, but KALYDECO itself has not received marketing authorization or NDA approval from any regulatory authorities.

Expanded Access Programs for KALYDECO

An expanded access program for KALYDECO is currently open at participating clinical trial sites in the United States. This program is designed to provide KALYDECO to people ages 6 and older who have at least one copy of the G551D mutation, are in critical medical need and may benefit from treatment prior to potential FDA approval in the United States.

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 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.

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 www.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 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 with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

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