RT Journal Article
SR Electronic
T1 Late-breaking abstract: VX-770, an investigational CFTR potentiator, in subjects with CF and the G551D mutation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4655
VO 38
IS Suppl 55
A1 Barry J. Plant
A1 Bonnie Ramsey
A1 Karl Yen
A1 Qunming Dong
A1 Sally Rodriguez
A1 J. Stuart Elborn
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/4655.abstract
AB Background: Restoring dysfunctional CFTR mediated ion transport is a potential treatment for CF. VX-770, a CFTR potentiator, is designed to increase CFTR ion transport activity.Aims and objectives: This Phase 3 study evaluated the efficacy and safety of VX-770 in subjects with CF who have the G551D mutation on at least one CFTR allele.Methods: A randomized, double-blind, placebo-controlled trial of subjects ≥12 years of age who received oral VX-770 150 mg q12h (n=83) or placebo (n=78) for up to 48 weeks.Results: The mean absolute change from baseline through Week 24 in % predicted FEV1 (primary endpoint), improved by 10.4% in the VX-770 group, while the placebo group decreased by 0.2% (P<0.0001). This reflected a mean increase of 361 mL (P<0.0001) and a mean relative change from baseline of 16.9% of predicted FEV1 (P<0.0001) in the VX-770 group compared to placebo. Improvement in FEV1 with VX-770 was evident at Day 15 and maintained through Week 48, at which time the VX-770 group showed an improvement of 10.1% (366 mL change) while the placebo group had a decrease of 0.4% (7 mL change). A 55% reduction in the risk of pulmonary exacerbations (P=0.0012) was observed through 48 weeks with VX-770 treatment. The reduction from baseline in sweat chloride, a biomarker of CFTR activity, was –48.1 mmol/L through Week 48 in the VX-770 group compared to placebo (P<0.0001). The safety profile of VX-770 was comparable to placebo.Conclusions: VX-770 demonstrated a clinically relevant and statistically significant improvement in pulmonary function and reduction in pulmonary exacerbations and sweat chloride up to 48 weeks of treatment. The safety profile was similar to placebo.Supported by Vertex