Vertex’s Ivacaftor Benefits Residual Function Mutation Cystic Fibrosis Patients in First-of-Kind Study

Vertex Pharmaceuticals‘ two-part proof-of-concept study evaluating ivacaftor (under the name KALYDECO) in 24 cystic fibrosis patients shows data consistent with previous preclinical observations. An eight-week open-label period resulted in improved lung function in patients, initiating plans for a future Phase 3 trial.

Each of the 24 patients had a residual function mutation. More than 3,000 North Americans, Europeans, and Australians have a non-R117H residual function mutation, allowing results to be extrapolated to numerous other patients. “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, MD, Senior Vice President and Chief Medical Officer of Vertex, in a news release. “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.”

This study was the first of its kind to use ivacaftor in cystic fibrosis patients with multiple residual function mutations. The first part consisted of two, two-week treatment cycles of ivacaftor followed by two treatment cycles of placebo, or vice-versa. A four-week washout period was between ivacaftor and placebo cycles. Treatment with ivacaftor significantly increased percent predicted forced expiratory volume in one second (PPFEV1) compared to placebo. The mean absolute improvement in FEV1 was 2.3 percentage points compared to placebo.

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The second part was an eight-week open-label study allowing all patients access to ivacaftor. Again, patients saw an increased PPFEV1, indicating improved lung performance. Additionally, a mean decrease of 15.7 mmol/L in sweat chloride was also seen after the eight weeks. Ivacaftor was well-tolerated by patients, and the most common side effects were cough and respiratory tract infection.

Ivacaftor works to enhance the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in cells that are still able to produce CFTR. The type of residual mutation determines if defective CFTR proteins or just fewer CFTR proteins are produced. Unlike other medicines, ivacaftor treats the cause of cystic fibrosis, rather than only symptoms.