Study Results

• What We Learned:

  This study found that there was a significant improvement in lung function and in sweat chloride after four weeks in participants who have one copy of F508del and one copy of a minimal function CFTR mutation and were receiving 200mg or 600mg of VX-440 in combination with ivacaftor/VX-661. Additionally, there was significant improvement in lung function and in sweat chloride in participants who have two copies of the F508del CFTR mutation and were receiving 600mg of VX-440 in combination with ivacaftor/VX-661. Overall, VX-440 in combination with ivacaftor/VX-661 was well-tolerated. Elevated liver enzymes were observed in two participants receiving the VX-440 600 mg dose; this led to early discontinuation of the study in one of these participants. 

   

  Vertex elected to move forward with a different compound for future development of their triple combination modulator therapy. 

• Primary Findings:

  Effectiveness:

  The primary objectives of the study were safety, tolerability, and efficacy as measured by lung function (absolute change in ppFEV1 from baseline). Overall, VX-440 in combination with ivacaftor/VX-661 was well-tolerated. There was one discontinuation in the VX-440 600mg group due to elevated liver enzymes > 5x the upper limit of normal and one in the control group due to abnormal respiration and increased sputum. Additionally, one participant in the VX-440 600mg group experienced elevated liver enzymes (> 8x upper limit of normal) on the last day of dosing. Both participants who experienced elevated liver enzymes while on the triple combination therapy returned to normal after discontinuation of VX-440.

   

  In Part 1 and 2, changes in lung function (measured by mean absolute change in FEV1 percent of predicted) and sweat chloride were also measured.

   

  In Part 1 (F508del and minimal function group), 47 participants (N=18 at 200mg, N=18 at 600mg, N=11 in placebo) were enrolled. There was a significant improvement in lung function at both the 200mg and 600mg doses (+10% and +12% respectively, p<0.0001) and a significant reduction in sweat chloride at both doses (-20.7 and -33.1, p<0.0001) when compared to placebo. Additionally, there was a significant improvement in a patient-reported outcome questionnaire, measured by mean absolute change in the respiratory section of CFQ-R (18.3 points at 200mg and 20.7 points at 600mg), when compared to placebo.

   

  In Part 2 (F508del/F508del group), 26 participants (N=20 at 600mg, N=6 in placebo) were enrolled. There was a significant improvement in lung function at the 600mg dose (+9.5%, p<0.0001) and a significant reduction in sweat chloride (-31.3, p<0.0001) when compared to placebo.

   

  These results have been provided from a Vertex Press Release and from the clinicaltrials.gov posting. 

   

  Safety:

• Citation:

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