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VX-770
(Cystic Fibrosis)

Cystic Fibrosis (CF) affects about 30,000 people in the United States and approximately 70,000 people worldwide. Cystic fibrosis is caused by genetic mutations that result in a malfunctioning or missing Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) proteins on cell surfaces. These missing or malfunctioning CFTR proteins result in an imbalance of salt and water in the airways, causing a cascade of mucus plugging, infection and inflammation that characterizes CF. This cascade accounts for a large portion of the morbidity and mortality seen with CF.

VX-770, an investigational CFTR potentiator, is intended to increase chloride ion transport through the defective CFTR protein. 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.

Based on positive results announced in 2008 from a Phase 2 trial of VX-770 in patients with CF who carry the G551D mutation in CFTR, Vertex initiated a Phase 3 registration program designed to support registration of VX-770 in patients with the G551D mutation. The G551D mutation is present in approximately 4% of CF patients.

The VX-770 registration program will consist of three clinical trials:

1. A randomized, placebo-controlled, double-blind, parallel-group Phase 3 study of VX-770 in patients with CF aged 12 years and older with the G551D mutation on at least one allele. The trial is expected to enroll a minimum of 80 patients who will receive either VX-770 or placebo for 48 weeks. In the trial, VX-770 will be dosed as a single 150mg tablet twice daily. The primary endpoint is absolute change from baseline in percent predicted FEV₁ through week 24. Patients who complete the 48-week trial may have the option to enroll in a roll-over study following completion of 48 weeks of treatment in the trial. The trial is currently open to patient enrollment, and Vertex expects the trial to be fully enrolled in the first quarter of 2010.

2. A two-part, randomized, placebo-controlled, double-blind, parallel-group Phase 3 study of VX-770 in patients with CF aged 6 to 11 years with the G551D mutation on at least one allele. Part 1 of the trial is a single-dose pharmacokinetic study that is expected to enroll approximately 10 patients. Following an analysis of data from Part 1, Part 2 of the trial will enroll approximately 30 patients who will receive either VX-770 or placebo for 48 weeks. In the trial, VX-770 will be dosed nominally as a single 100mg tablet twice daily, following confirmation of the pharmacokinetic profile of VX-770 in patients aged 6 to 11 years. The primary endpoint of the trial is absolute change from baseline in percent predicted FEV₁ through week 24. Patients who complete the 48-week trial may have the option to enroll in a roll-over study following completion of 48 weeks of treatment in the trial. Patient enrollment in Part 1 of the trial is expected to open in the second quarter of 2009.

3. A randomized, placebo-controlled, double-blind, parallel-group Phase 2 study of VX-770 in patients with CF aged 12 years and older who are homozygous for the F508del mutation. The trial is expected to enroll approximately 120 patients who will receive either VX-770 or placebo for 16 weeks. In the trial, VX-770 will be dosed as a single 150mg tablet twice daily. The primary endpoints of the trial are safety as well as absolute change from baseline in percent predicted FEV₁ through week 16. Patient enrollment in the trial is expected to begin in the third quarter of 2009.

The primary endpoint for patients with the G551D mutation will be FEV₁, which will be measured through 24 weeks. Additional FEV₁ measurements will be taken through 48 weeks as a secondary endpoint for patients with the G551D mutation to assess durability of the response. The trials in patients with the G551D mutation will be conducted for 48 weeks to gain additional safety data in G551D patients. For patients with the F508del mutations, the primary endpoints will be safety and FEV₁, which will be measured through 16 weeks. Additional secondary endpoints, including sweat chloride, will be measured in each trial to evaluate the effect of VX-770 on improving the function of the defective CFTR protein. The trials will be conducted at approximately 110 clinical trial sites in North America, Europe and Australia.