Combo Tx Significantly Improves Lung Function in Cystic Fibrosis Study

A total of 477 were enrolled, the treatment group received tezacaftor once daily in combination with ivacaftor
A total of 477 were enrolled, the treatment group received tezacaftor once daily in combination with ivacaftor

Vertex announced results from two Phase 3 trials of their investigational ivacaftor/tezacaftor (VX-661) combination treatment for cystic fibrosis (CF) patients who have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Ivacaftor (Kalydeco; Vertex) is currently approved to treat cystic fibrosis patients aged ≥2 years, who have one of G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutated cystic fibrosis genes. Tezacaftor is a treatment designed to address the processing defect of F508del-CFTR to help it reach the cell surface where ivacaftor can further enhance the protein's function.

EVOLVE was a randomized, double-blind, placebo-controlled study that evaluated the combination in CF patients who have two copies of the F508del gene mutation. The primary endpoint was mean absolute improvement in ppFEVfrom baseline through Week 24. A total of 477 patients were enrolled and the treatment group received tezacaftor 100mg once daily in combination with ivacaftor 150mg every 12 hours for 24 weeks.

Results showed that the ivacaftor/tezacaftor group reached the primary endpoint with a mean absolute improvement in ppFEVof 4% points from baseline vs. placebo (P<0.0001). 

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The second study, EXPAND, was a randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the combination treatment in patients who have 1 mutation that results in residual CFTR function and 1 F508del mutation. Patients were randomized to 1 of 6 groups to receive tezacaftor/ivacaftor, ivacaftor monotherapy or placebo for eight weeks, followed by an 8-week washout period. The primary endpoints were absolute change in ppFEV1 from baseline to the average of the Week 4 and Week 8 measurements.

Results showed that the mean absolute improvement in ppFEV1 for the treatment group was  6.8% points from baseline vs. placebo (P<0.0001) and was 4.7% points vs. placebo in patients taking ivacaftor alone. 

In both studies, the tezacaftor/ivacaftor combination treatment was well tolerated. The most common adverse events were infective pulmonary exacerbation and cough. 

Based on both study's results, Vertex plans to submit a New Drug Application (NDA) for the tezacaftor/ivacaftor combination to the U.S. Food and Drug Administration (FDA) sometime in the third quarter of 2017.

For more information call (877) 634-8789 or visit vrtx.com.