Strive trial showed VX-770 boosts lung function in patients with at least one G551D mutation.

Vertex Pharmaceuticals confirmed plans to submit approval applications for its cystic fibrosis therapy candidate VX-770 to both the U.S. and European regulatory authorities later this year, on the back of positive data from a pivotal Phase III study and Phase II safety trial, both reported today.

The 48-week Phase III Strive study was designed to evaluate the CFTR potentiator VX-770 specifically in patients with at least one copy of the G551D mutation. 161 patients were enrolled. The results found that in comparison with placebo, therapy using VX-770 led to a 17% relative mean improvement in lung function (measured as FEV1) from baseline, and a mean absolute improvement from baseline of approximately 10.5%. Benefits were sustained over the whole 48 weeks of the study.

Strive also showed that in comparison with placebo-treated patients, those receiving VX-770 were 55% less likely to experience a pulmonary exacerbation, and managed to gain weight. VX-770 therapy was also associated with a significant reduction in salt in the sweat. Vertex points out that sweat chloride is a diagnostic hallmark of CF that represents a marker for CFTR protein dysfunction.

“Treating the underlying cause of cystic fibrosis with VX-770 led to clinical improvements that were far beyond our expectations,” remarks Peter Mueller, Ph.D., Vertex’ CSO and executive vp for global R&D. “All primary and key secondary outcome measures in this study supported VX-770 over placebo. Patients’ lung function improved, they gained weight, experienced fewer respiratory symptoms, and felt substantially better.”

VX-770 is a CFTR potentiator designed to boost the function of defective CFTR proteins by increasing the gating activity of CFTR at the cell surface.  The registrational program for the drug includes three trials: the Phase III Strive study; the Phase III Envision study, in children aged 6-11 years with at least one copy of the G551D mutation; and the Phase II Discover study, in CF patients who are homozygous for the F508del mutation, which prevents the CFTR protein from moving to its proper location at the cell surface.

Data from Envision is expected during mid-2011, but results from the 16-week Phase II Discover trial were also reported today. These demonstrated no safety issues associated with VX-770 therapy. Adverse events were similar between the treatment and placebo groups. The trial did suggest that in patients who were homozygous for the F508del mutation, VX-770 therapy resulted in no clinically meaningful improvements in lung function.  “Based on the results of Discover, we continue to believe the combination of a potentiator and corrector may be the best approach to treating people with two copies of the F508del mutation,” notes Robert Kauffman, M.D., svp and CMO at Vertex.

To this end, Vertex is already carrying out a Phase IIa trial evaluating treatment regimens that combine VX-770 with VX809, the firm’s CFTR corrector candidate designed to increase CFTR function by increasing the trafficking of CFTR to the cell surface. Data from the study is anticipated during 2011.

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