Vertex Ivacaftor Press Release

Two 24-Week Phase 3 Studies of Lumacaftor in Combination with Ivacaftor Met Primary Endpoint with Statistically Significant Improvements in Lung Function (FEV1) in People with Cystic Fibrosis who have Two Copies of the F508del Mutation

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-Combination of lumacaftor and ivacaftor is the first regimen designed to treat the underlying cause of CF in people with two copies of the F508del mutation, the most common form of the disease-

-All four 24-week treatment arms achieved primary endpoint of mean absolute improvement in FEV1 compared to placebo, with a range of 2.6 to 4.0 percentage points (p0.0004); mean relative improvement of 4.3% to 6.7% (p0.0007)-

-Pooled analysis of Phase 3 studies showed statistically significant reductions of 30 and 39 percent in rate of pulmonary exacerbations for those who received the combination regimens compared to those who received placebo (p0.0014)-

-The combination regimens were generally well tolerated; 4.2 percent of patients receiving the combination regimens discontinued treatment due to adverse events compared to 1.6 percent of patients who received placebo; more than 1,000 patients have entered the rollover study to receive a combination regimen-

BOSTON–(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from two Phase 3 studies of lumacaftor in combination with ivacaftor that showed statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV1) in people ages 12 and older with cystic fibrosis (CF) who have two copies (homozygous) of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. All four 24-week combination treatment arms in the studies, known as TRAFFIC and TRANSPORT, met their primary endpoint of mean absolute improvement in ppFEV1 from baseline compared to placebo at the end of treatment. Mean absolute improvements in ppFEV1 of between 2.6 and 4.0 percentage points from baseline compared to placebo were observed across the studies (p≤0.0004), with mean relative improvements of 4.3 percent to 6.7 percent (p≤0.0007).

The combination regimens were generally well tolerated. The most common adverse events, regardless of treatment group, were infective pulmonary exacerbation, cough, headache and increased sputum. 4.2 percent of patients who received the combination regimens discontinued treatment because of adverse events compared to 1.6 percent of those who received placebo. More than 1,000 patients have entered a rollover study to receive a combination regimen.

Data from a pre-specified pooled analysis showed improvements in multiple key secondary endpoints. For patients who received the combination regimens compared to those who received placebo, there were statistically significant reductions in the rates of pulmonary exacerbations and statistically significant improvements in both body mass index and the proportion of patients with at least a 5 percent relative improvement in ppFEV1. Statistically significant changes were not consistently observed for patient-reported respiratory symptoms as reported in the CF questionnaire-revised (CFQ-R).

Based on these data, Vertex plans to submit regulatory applications for approval in multiple countries, including a New Drug Application (NDA) in the United States and Marketing Authorisation Application (MAA) in Europe, in the fourth quarter of 2014 for people with CF ages 12 and older who have two copies of the F508del mutation.

“On average, people with CF who have two copies of the F508del mutation lose nearly two percent of their lung function each year, underscoring the urgent need for new medicines that address the underlying cause of this disease,” said Bonnie Ramsey, M.D., Professor of Pediatrics, University of Washington School of Medicine, Director of the Center for Clinical and Translational Research at Seattle Children’s Research Institute and a lead Principal Investigator for TRANSPORT. “These data showed consistent evidence of clinical benefit in lung function and other measures of the disease. The significant improvements in pulmonary exacerbations are particularly important given the potential for these events to result in hospitalizations, permanent lung damage and the need for additional treatment with antibiotics and other medicines.”

“The combination of lumacaftor and ivacaftor is the first regimen designed to address the underlying cause of CF for people with the most common form of the disease, and based on these data, we plan to move as fast as possible to submit applications for approval of this combination regimen in countries around the world,” said Jeffrey Chodakewitz, M.D., Senior Vice President and Chief Medical Officer at Vertex. “I would like to thank the more than 1,100 people who took part in these studies worldwide, as well as their families, friends and caregivers.”

“These data mark an exciting day for the CF community and validate our more than 30-year commitment to develop medicines that target the underlying basic defect of cystic fibrosis for all people with this devastating disease,” said Robert J. Beall, Ph.D., President and CEO, Cystic Fibrosis Foundation. “While we await the FDA’s review of these data, we’re grateful to the many people with CF, families and volunteers who have committed their time and resources to help accelerate our efforts to bring effective therapies to all people living with the disease.”

Cystic fibrosis is a rare genetic disease for which there is no cure. CF is caused by defective or missing CFTR proteins at the cell surface that result from mutations in the CFTR gene. The defective function or absence of CFTR proteins in people with CF results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. In people with two copies of the F508del mutation, the CFTR protein is not processed, or folded, normally within the cell and generally does not reach the cell surface. Lumacaftor is designed to address the processing defect of F508del-CFTR to enable it to reach the cell surface where ivacaftor can further enhance the protein’s function. In North America, Europe and Australia, there are more than 22,000 people ages 12 and older who have two copies of the F508del mutation.

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