Vertex Pharmaceuticals Incorporated, a global biotechnology company that aims to discover, develop and commercialize innovative medicines,  announced the results of a two-part proof-of-concept study of ivacaftor in 24 people with cystic fibrosis (CF) who have a residual function mutation.

The first part of the study evaluated ivacaftor, compared with placebo, in a two-week crossover design over two treatment cycles, and the second part of the study evaluated ivacaftor in an eight-week open-label design. In part one, a statistically significant improvement in mean absolute lung function (percent predicted forced expiratory volume in one second; PPFEV1) was observed after treatment with ivacaftor for two weeks compared with placebo.

In part two of the study, improvements in lung function (PPFEV1) were observed after eight weeks of treatment. In the study, ivacaftor was generally well-tolerated, and the most common adverse events in the treatment group were cough and respiratory tract infection.

This proof-of-concept study was the first to evaluate the use of ivacaftor in multiple residual function mutations and is supported by in vitro observations that showed ivacaftor enhanced the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in cells with residual function mutations. Based on these data, Vertex plans to initiate a larger Phase 3 study in people with residual function mutations that will evaluate longer-duration treatment with ivacaftor, pending discussions with regulatory authorities.

There are more than 3,000 people ages 6 and older in North America, Europe and Australia who have a non-R117H residual function mutation.

"This study showed potential for ivacaftor to provide clinical benefit for many of the people who have a residual function mutation and provides important support for the initiation of a Phase 3 study in people with these mutations," said Jeffrey Chodakewitz,  managing direcrtor, senior vice president and chief medical officer at Vertex. "While this was a small proof-of-concept study, these data are another step forward in our commitment to expand the number of people who can benefit from ivacaftor."

The first part of the study included two randomised, double-blind, placebo-controlled treatment cycles (part one), and the second part of the study was an eight-week open-label period (part two). In part one, patients received ivacaftor for two, two-week treatment cycles and placebo for two, two-week treatment cycles as part of a multiple within-patient crossover design. In the first treatment cycle of part one, patients received either ivacaftor or placebo for two weeks, which was immediately followed by the opposite treatment (placebo or ivacaftor) for two weeks. The treatment cycles were separated by a four-week washout period, and in the second treatment cycle of part one, patients received either ivacaftor or placebo for two weeks, immediately followed by the opposite treatment (placebo or ivacaftor) for two weeks. Part two of the study, the open-label evaluation, was separated from the second treatment cycle by a four-week washout period, and all patients received ivacaftor in this part of the study.

The primary endpoint analysis was based on part one of the study and evaluated the mean absolute change from baseline in lung function (percent predicted forced expiratory volume in one second; PPFEV1) at the end of two weeks of treatment versus placebo. The study enrolled 24 people age 12 and older with a residual function mutation. All people with a residual function mutation have some functioning CFTR protein. Depending on the specific mutation, residual function mutations can result in defective CFTR proteins at the cell surface and/or a reduced number of CFTR proteins at the cell surface.