Two Phase III studies reported of tezacaftor (VX-661) / ivacaftor combination of cystic fibrosis transmembrane conductance regulator (CFTR) gene affected patients.-Vertex

Vertex Pharmaceuticals Incorporated announced results from two Phase III studies of the tezacaftor (VX-661) / ivacaftor combination treatment that showed statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV1) in people with cystic fibrosis (CF) ages 12 and older who have certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

The 24-week EVOLVE study evaluated the combination treatment in people who have two copies of the F508del mutation. This study met its primary endpoint with a mean absolute improvement in ppFEV1 through 24 weeks of 4.0 percentage points from baseline compared to placebo (p < 0.0001). The second study, EXPAND was an 8-week crossover study that evaluated the combination treatment in people who have one mutation that results in residual CFTR function and one F508del mutation. This study met the primary endpoints of absolute change in ppFEV1 from baseline to the average of the Week 4 and Week 8 measurements, with the tezacaftor/ivacaftor combination treatment demonstrating a mean absolute improvement of 6.8 percentage points compared to placebo (p < 0.0001) and the ivacaftor monotherapy group demonstrating a mean absolute improvement of 4.7 percentage points compared to placebo (p < 0.0001). Based on these results. Across both studies, the tezacaftor/ivacaftor combination treatment was generally well tolerated.

The most common adverse events, regardless of treatment group, were infective pulmonary exacerbation and cough. In both studies, rates of discontinuations due to adverse events were low and similar between placebo and treatment groups (2.1% for placebo vs 1.7% for the tezacaftor/ivacaftor combination). Rates of respiratory adverse events were similar between placebo and treatment groups (15.0% for placebo vs 11.4% for the tezacaftor/ivacaftor combination).