Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced data from a Phase 2 study of VX-661 and 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, known as F508del. The study evaluated four dose levels of VX-661 (10, 30, 100 and 150 mg) dosed once daily for 28 days in combination with ivacaftor (150 mg) dosed twice daily. The study also evaluated a separate group of patients who received VX-661 (10, 30, 100 and 150 mg) dosed without ivacaftor for 28 days. Dose-dependent, mean relative improvements in lung function (percent predicted forced expiratory volume in one second; FEV1), both within group and versus placebo, were observed across the combination dosing groups. Patients in the 100 and 150 mg combination dose groups showed statistically significant mean relative improvements in lung function, versus placebo, of 9.0 percent>1 across the combination dose groups returned toward baseline during the post-treatment 28-day washout period. VX-661 was generally well-tolerated, both as monotherapy and in combination with ivacaftor, and most adverse events were mild to moderate in severity and similar between the treatment groups and those who received placebo. Vertex plans to conduct additional studies of VX-661 to further evaluate its potential for late-stage development, pending regulatory discussions.
“With these data and the recent initiation of a Phase 3 program for a combination of our lead CFTR corrector VX-809 with ivacaftor, we are making significant progress toward our goal to help many more people with CF.”
"This first study of VX-661 and ivacaftor provides further validation of the strategy of combining a corrector and potentiator to improve lung function in people with the most common type of cystic fibrosis," Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "With these data and the recent initiation of a Phase 3 program for a combination of our lead CFTR corrector VX-809 with ivacaftor, we are making significant progress toward our goal to help many more people with CF."
Cystic fibrosis is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. In people with two copies of the most common mutation in the CFTR gene, F508del, little to no CFTR protein reaches the cell surface. VX-661, known as a CFTR corrector, is believed to help CFTR protein reach the cell surface. Ivacaftor, known as a CFTR potentiator, keeps cell surface CFTR protein channels open longer to increase the flow of salt and water. Worldwide, nearly half of people with CF have two copies of the F508del mutation and an additional one-third have one copy of the F508del mutation.
Lung Function Results for Combination Dosing
Mean absolute and relative improvements in lung function were observed in all the combination dosing groups (10, 30, 100 and 150 mg), both within group and versus placebo. The improvements in lung function were dose dependent, with the greatest improvements observed in the groups that received the highest doses of VX-661 in combination with ivacaftor. Patients in the two highest combination dose groups (VX-661 100 mg or 150 mg in combination with ivacaftor 150 mg) showed statistically significant mean relative improvements in lung function, versus placebo, of 9.0 percent>1 were observed early in treatment, and the mean relative FEV1 improvements, versus placebo, for the highest combination group (VX-661 150 mg in combination with ivacaftor 150 mg) were statistically significant at Days 14, 21 and 28. The mean relative FEV1 across the combination dose groups returned toward baseline during the post-treatment 28-day washout period. Additional lung function results are noted below:
NS = Not Statistically Significant
* The statistical analysis plan (SAP) for this study did not include statistical comparisons for the 28-day washout period