Final Data from Phase 2 Combination Study of VX-809 and KALYDECO(TM) (ivacaftor) Showed Statistically Significant Improvements in Lung Function in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation

CAMBRIDGE, Mass., Jun 28, 2012 --- Adverse events were similar between treatment and placebo groups; most events were mild to moderate -

--- Pivotal program to evaluate VX-809 (600mg) in combination with KALYDECO (250mg) planned to start in early 2013, pending discussions with regulatory agencies -

Vertex Pharmaceuticals Incorporated announced today final data from a Phase 2 study of VX-809 and KALYDECO(TM) (ivacaftor) that showed statistically significant improvements in lung function among adults with cystic fibrosis (CF) who have two copies (homozygous) of the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del. The study randomized homozygous F508del patients to three treatment groups that evaluated increasing doses of VX-809 (200mg, 400mg or 600mg; QD) alone for 28 days, followed by VX-809 in combination with KALYDECO (250mg; q12h) from Day 28 to 56. When patients received the two medicines in combination (Day 28 to 56), there was a statistically significant improvement in lung function (percent predicted forced expiratory volume in one second, FEV1) in each of the homozygous treatment groups compared to placebo. The greatest improvements in lung function were observed in patients who received 600mg of VX-809, the highest dose evaluated in this study, in combination with KALYDECO. These data support Vertex's plans to initiate a pivotal program in early 2013, which is expected to evaluate VX-809 (600mg) in combination with KALYDECO (250mg) in homozygous patients, pending discussions with regulatory agencies. Most adverse events observed during the 56-day study were mild to moderate in severity across all treatment groups and similar between treatment and placebo groups.

The study also included an exploratory treatment group that looked at a subset of heterozygous patients who have one copy of the F508del mutation and a second mutation that is not expected to respond to KALYDECO dosed as monotherapy. This group of patients received VX-809 (600mg) and KALYDECO on the same dosing schedule as homozygous patients. Heterozygous patients who were treated with the combination experienced a mean absolute improvement in lung function compared to placebo from Day 28 to 56. Based on these data, Vertex plans to conduct additional clinical studies of VX-809 and KALYDECO in heterozygous patients.

"We are focused on developing additional medicines to treat the underlying cause of cystic fibrosis, and these data represent exciting progress toward that goal," said Chris Wright, M.D., Ph.D., Vertex's Senior Vice President, Global Medicines Development and Medical Affairs. "The data announced today show that the addition of KALYDECO to VX-809 resulted in improvements in lung function and support our plans to start a pivotal program in people with cystic fibrosis who have two copies of the most common CFTR mutation in early 2013."

Michael P. Boyle, M.D, FCCP, Associate Professor of Medicine, Director of the Johns Hopkins Adult Cystic Fibrosis Center, and lead investigator for this study commented, "I am particularly encouraged with these results given the significant improvements in lung function when cystic fibrosis patients with two copies of the F508del mutation went from receiving VX-809 alone to combination treatment with KALYDECO and look forward to the start of the pivotal program."

Vertex will host a conference call for investors and media today, June 28, 2012 at 8:00 a.m. ET, to discuss these data. Full data from this study will be submitted for presentation at an upcoming medical meeting.

Study Results

This is a Phase 2 randomized, double-blind, placebo-controlled study. Data from the first part of this study (Cohort 1) were announced in 2011 and an interim analysis of the second part (Cohort 2) was announced in May 2012. Today's announcement includes final data from the second part of this study that enrolled 109 people with CF ages 18 and older with one or two copies of the F508del mutation. Patients were divided into five treatment groups of approximately 20 patients each. Three groups of homozygous patients were randomized to receive VX-809 alone (200mg, 400mg or 600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. One group of heterozygous patients received VX-809 alone (600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. The placebo group included both homozygous and heterozygous patients.

LUNG FUNCTION: PATTERN OF RESPONSE

Progressive lung disease is a major source of illness and is the primary cause of death in people with CF. Typically, people with CF lose 1 percent to 2 percent of their lung function (FEV1) each year.

During the first 28 days of the study, there was a decline in lung function in the majority of patients in both the treatment and placebo groups. In contrast, from Day 28 to 56, when the treatment groups received the combination of VX-809 and KALYDECO, there was a mean absolute improvement in lung function in each of the treatment groups, while lung function continued to decline for the placebo group.

HOMOZYGOUS PATIENTS RECEIVING VX-809 -- 600mg

Lung Function: Homozygous patients treated with the highest dose of VX-809 (600mg) in combination with KALYDECO from Day 28 to 56 experienced a mean absolute improvement in lung function of 8.6 percentage points compared to placebo (p<0.001) and a mean absolute improvement of 6.1 percentage points within group (p<0.001). Fifty-five percent of these patients experienced an absolute improvement in lung function of 5 percentage points or more compared to 9.5 percent of those treated with placebo. Twenty-five percent experienced an absolute improvement of 10 percentage points or more compared to 0 percent of those treated with placebo.

Mean Absolute Changes in Lung Function (percent predicted FEV1)

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