The CFTR potentiator icenticaftor for treatment of bronchiectasis: an international phase 2, double-blind, randomized placebo-controlled trial

To the Editor: Impaired mucociliary clearance is the core mechanism of bronchiectasis.1 Bacterial infections contribute to poor quality of life and clinical outcomes.2 Bronchiectasis is a key feature of cystic fibrosis, caused by inherited dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR). Some patients with bronchiectasis may have CFTR-related disorders, whereas acquired CFTR dysfunction results from airway inflammation and neutrophil-derived proteases.3 The CFTR potentiator icenticaftor (QBW251) may augment wild-type CFTR function.4 In clinical trials, icenticaftor modestly improved lung function in stage II-III chronic obstructive pulmonary disease (COPD)5,6 and decreased bacterial load and plasma fibrinogen.7 Between February 2021 and June 2023, we conducted a randomized, double-blind, placebo-controlled phase 2 trial to assess the effects of icenticaftor in bronchiectasis. Patients were enrolled from (number of sites) the United Kingdom (7), Spain (2), Germany (3), and China (2). Key inclusion criteria were: patients aged ≥18 years; bronchiectasis diagnosed by chest high-resolution computed tomography (HRCT); remaining stable for ≥4 weeks; had productive cough on >50% of days for ≥3 consecutive months within 12 months; and bacterial load of ≥106 colony-forming unit (CFU)/mL with ≥1 potentially pathogenic microorganism. We excluded current smokers, patients with severe emphysema, cystic fibrosis, and tuberculosis, or those on long-term oxygen therapy.