Study Results

• What We Learned:

  In a population with F508del plus either a gating or residual function mutation, treatment with the 3-drug combination of elexacaftor/tezacaftor/ivacaftor for 8 weeks resulted in higher ppFEV1 and more normal sweat chloride concentration when compared with an active control group receiving ivacaftor alone or tezacaftor/ivacaftor treatment. No significant safety concerns were identified in this study of the 3-drug modulator elexacaftor/tezacaftor/ivacaftor.

• Primary Findings:

  Effectiveness:

  This study was completed in July 2020. The study enrolled 258 patients ages 12 years and older with F508del-gating or F508del-residual function genotypes. After 4 weeks run-in with ivacaftor or tezacaftor/ivacaftor, patients were randomized to continue this modulator treatment alone (active control group) or to receive elexacaftor/tezacaftor/ivacaftor for 8 weeks.

   

  The primary outcome was change in percent predicted FEV1 over the 8-week period, comparing the active control modulator started during the run-in period with the 3-drug combination of elexacaftor/tezacaftor/ivacaftor. The 8-week change in ppFEV1 was significantly greater in those receiving triple combination modulator ppFEV1. The average difference was 3.5 percentage points.

   

  A key secondary outcome was the change in sweat chloride concentration over the same 8-week treatment period. The change in sweat chloride concentration was significantly greater in the group receiving triple combination modulator compared with the active control groups. The average difference in sweat chloride change between the two groups was 23.1 mmol/L.

  Safety:

  The number of all adverse events and treatment-related adverse events were not significantly different between the groups.

• Citation:

  N Eng J Med 2021;DOI 0.1056/NEJMoa2100665;385:815-825

For current information about the overall development status of this drug, please check the Drug Development Pipeline.