Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy with tezacaftor-ivacaftor or with ivacaftor alone may be effective therapy in patients with cystic fibrosis who are heterozygous for the Phe508del deletion and CFTR residual-function mutation, according to a study published in the New England Journal of Medicine.
Researchers performed a phase 3, double-blinded, placebo-controlled, 2-period, 3-intervention crossover trial during the course of approximately 2 years to evaluate the safety and efficacy of monotherapy with ivacaftor or in combination with tezacaftor in 248 patients with cystic fibrosis ≥12 years of age and heterozygous for the Phe508del mutation.
Participants were randomly assigned to receive 1 of 6 sequences including an 8-week intervention, followed by an 8-week washout period, followed by another 8-week intervention. The primary end point of the study was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to the average at week 4 and week 8.
Study results showed 6.8 and 4.7 percentage points difference of the least-squares mean difference vs placebo with respect to the absolute change in the percentage of predicted FEV1 in participants treated with tezacaftor-ivacaftor and ivacaftor alone, respectively (P <.001).
Investigators concluded that treatment with CFTR modular therapy with the tezacaftor-ivacaftor combination therapy or ivacaftor monotherapy was efficacious in patients with cystic fibrosis heterozygous for the Phe508del deletion and CFTR residual-function mutation, and should be considered as prospective treatment options by clinicians.
In addition, treatment with tezacaftor-ivacaftor treatment was safe, with no new risks identified and no treatment discontinuations during the study.
Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis [published online on November 3, 2017]. N Engl J Med. doi:10.1056/NEJMoa1709847