Vertex Pharmaceuticals announced results from two Phase 3 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, Vertex plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the third quarter of 2017 for the tezacaftor/ivacaftor combination treatment in people with CF ages 12 and older who have two copies of the F508del mutation and in people who have one mutation that results in residual CFTR function and F508del mutation. Vertex will host a conference call for investors tomorrow, March 29, 2017 at 8:00 a.m. EDT, to discuss 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).
“The tezacaftor/ivacaftor combination treatment demonstrated clinically meaningful benefits, with a favorable safety profile, across multiple patient groups,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. “This combination treatment may provide a promising new option for treating the underlying cause of CF in the future and brings us increasingly closer to our goal of developing new medicines for all people with the disease.”