Positive Phase 3 Study for Tezacaftor/Ivacaftor Combination in Children Aged 6-11 Years with Cystic Fibrosis Supports European Medicines Agency Submission - Seite 2

The primary endpoint of the study was the within-group absolute change in lung clearance index (LCI_2.5) from baseline through Week 8 in patients treated with tezacaftor/ivacaftor. LCI_2.5 measures the efficiency of ventilation in the lungs by quantifying how many standard lung volumes it takes to reduce exhaled nitrogen to 2.5 percent of its starting value when breathing pure oxygen. LCI is considered a more sensitive measure to detect early lung disease than forced expiratory volume in one second (FEV₁). Higher LCI scores indicate poorer lung function. To participate in the study, children at an initial screening visit had to have an LCI_2.5 ≥7.5, which is considered the cutoff for abnormal gas exchange. In the study, 54 children that were treated with tezacaftor/ivacaftor experienced a mean within-group absolute improvement in LCI_2.5 of -0.51 through 8 weeks (p < 0.0001).

Overall, safety data were similar to those observed in previous studies of tezacaftor/ivacaftor. The most common adverse events (≥ 10%) among those patients receiving tezacaftor/ivacaftor were cough, headache, and productive cough. No serious adverse events or adverse events leading to treatment discontinuation or interruption were observed.

About Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.