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ARTICLE | Clinical News

Kalydeco ivacaftor: Phase III data

December 23, 2013 8:00 AM UTC

The double-blind, international Phase III KONDUCT trial in 69 CF patients >=6 years of age who have at least 1 copy of the R117H mutation in the CFTR gene showed that twice-daily 150 mg oral Kalydeco missed the primary endpoint of improving the mean absolute change in percent predicted FEV1 from baseline to week 24 vs. placebo. Specifically, the mean absolute improvement in percent predicted FEV1 at week 24 compared to placebo was 2.1% (p=0.2). Kalydeco also led to a mean relative improvement in percent predicted FEV1 from baseline to week 24 of 5% compared to placebo (p=0.06). Compared to baseline, Kalydeco led to a mean absolute improvement in percent predicted FEV1 of 2.6% at week 24 (p=0.03) and a mean relative improvement in percent predicted FEV1 of 4.8% at week 24 (p=0.01). On secondary endpoints, Kalydeco significantly reduced sweat chloride levels and improved patient-reported outcomes as measured by the respiratory domain of the CFQ-R vs. placebo. There were no significant differences in the frequency of pulmonary exacerbations or changes in BMI between treatment groups.

A pre-specified subgroup analysis of patients >=18 years of age (n=50) showed that Kalydeco led to a significant mean absolute improvement of 5% in percent predicted FEV1 from baseline to week 24 compared to placebo (p=0.01). Kalydeco also led to a significant mean relative improvement of 9.1% in percent predicted FEV1 from baseline to week 24 compared to placebo (p=0.008). Additionally, a significantly greater proportion of patients >=18 years of age who received Kalydeco achieved a mean absolute improvement in FEV1 of >=5% vs. placebo (54.2% vs. 15.4%, p=0.007). In patients ages 6-11 years (n=17), Kalydeco led to a mean absolute decline of 6.3% in percent predicted FEV1 from baseline to week 24 compared to placebo (p=0.03). Vertex said there were too few patients ages 12-17 years to make a statistical comparison for the age group (n=2). The mean baseline FEV1 for patients >=18 years of age was 65% compared to 96% for patients ages 6-11 years. Vertex said it plans to meet with FDA early next year to discuss a potential sNDA for Kalydeco to treat CF patients with the R117H mutation, but declined to disclose the specific age group for the indication that it would seek. According to Vertex, approximately 1,100 patients with CF ages >=6 years in North America, Europe and Australia have >=1 copy of the R117H mutation. In the U.S., about 300 patients with CF >=18 years of age have the R117H mutation. ...