Lumacaftor/Ivacaftor Combo Improves Lung Function in CF Patients
Findings reported from two phase III trials
Positive results have been announced from two phase III studies of lumacaftor (VX-809, Vertex Pharmaceuticals) in combination with ivacaftor (Kalydeco, Vertex). The trials showed statistically significant improvements in lung function (the percent predicted forced expiratory volume in 1 second [ppFEV1]) in patients 12 years of age and older with cystic fibrosis (CF) who had two copies (homozygous) of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene.
All four 24-week combination treatment arms in the two studies — TRAFFIC and TRANSPORT — met their primary endpoint of mean absolute improvement in ppFEV1 from baseline compared with that of placebo at the end of treatment. Mean absolute improvements in ppFEV1 of between 2.6 and 4.0 percentage points from baseline compared with placebo were observed across the studies (P = 0.0004), with mean relative improvements of 4.3% to 6.7% (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. Treatment discontinuation due to adverse events occurred in 4.2% of patients who received the combination regimens compared with 1.6% of those given 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 with those who received placebo, there were statistically significant reductions in the rates of pulmonary exacerbations and statistically significant improvements in both the body mass index and the proportion of patients with at least a 5% relative improvement in ppFEV1.
Based on these findings, regulatory applications for approval in multiple countries, including a new drug application (NDA) in the U.S., are expected in the fourth quarter of 2014 for CF patients 12 years of age and older who have two copies of the F508del mutation.
The TRAFFIC and TRANSPORT trials were global phase III, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy and safety of lumacaftor in combination with ivacaftor in CF patients aged 12 years and older with two copies of the F508del mutation. Each study included two combination treatment groups and one placebo group. In the combination treatment groups, lumacaftor was dosed at either 600 mg once daily or 400 mg every 12 hours (q12h) in combination with ivacaftor (250 mg q12h).
A total of 1,108 people were enrolled in the two studies (549 in TRAFFIC and 559 in TRANSPORT). All of the patients received at least one dose of study drug at clinical trial sites in North America, Europe, and Australia. The primary endpoint of both studies was the mean absolute change from baseline in ppFEV1 at the end of the 24-week treatment period, as assessed by the average change in lung function at weeks 16 and 24.
Source: Vertex Pharmaceuticals; June 24, 2014.