Background: Cystic fibrosis is because mutations within the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and nearly 90% of patients have a minumum of one copy from the Phe508del CFTR mutation. Inside a phase 2 trial involving patients who have been heterozygous for that Phe508del CFTR mutation along with a minimal-function mutation (Phe508del-minimal function genotype), the following-generation CFTR corrector elexacaftor, in conjunction with tezacaftor and ivacaftor, improved Phe508del CFTR function and clinical outcomes.

Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial to verify the effectiveness and safety of elexacaftor-tezacaftor-ivacaftor in patients 12 years old or older with cystic fibrosis with Phe508del-minimal function genotypes. Patients were at random allotted to receive elexacaftor-tezacaftor-ivacaftor or placebo for twenty-four days. The main finish point was absolute vary from baseline in number of predicted forced expiratory volume in 1 second (FEV1) at week 4.

Results: As many as 403 patients went through randomization and received a minumum of one dose of active treatment or placebo. Elexacaftor-tezacaftor-ivacaftor, in accordance with placebo, led to a portion of predicted FEV1 which was 13.8 points greater at 4 days and 14.3 points greater through 24 days, an interest rate of lung exacerbations which was 63% lower, a respiratory system domain score around the Cystic Fibrosis Questionnaire-Revised (range, to 100, with greater scores indicating a greater patient-reported quality of existence regarding respiratory system signs and symptoms minimum clinically important difference, 4 points) which was 20.2 points greater, along with a sweat chloride concentration which was 41.8 mmol per liter lower (P<0.001 for all comparisons). Elexacaftor-tezacaftor-ivacaftor was generally safe and had an acceptable side-effect profile. Most patients had adverse events that were mild or moderate. Adverse events leading to discontinuation of the trial regimen occurred in 1% of the patients in the elexacaftor-tezacaftor-ivacaftor group.