Vertex Pharmaceuticals Inc says results from two Phase 3 studies of its lumacaftor plus ivacaftor (Kalydeco) drug combination showed statistically significant improvements in lung function (ppFEV1) in cystic fibrosis patients (12+) who have two copies of the F508del mutation.

All four 24-week combination treatment arms in the studies met their primary endpoint of mean absolute improvement in ppFEV1 from baseline compared to placebo at the end of treatment, according to the company. Mean absolute improvements in ppFEV1 of between 2.6 and 4.0% from baseline compared to placebo were observed across the studies (p?0.0004), with mean relative improvements of 4.3% to 6.7% (p?0.0007).

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% 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 Authorization Application (MAA) in Europe, in the fourth quarter of 2014.

“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, MD, senior vice president and CMO 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.”

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.

“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, PhD, 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.”

More information on the study is available on the Vertex website.