Elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis harbouring two

Background: The European Medicines Agency has recently expanded the label of elexacaftor-tezacaftor-ivacaftor (ETI) to all people with cystic fibrosis (pwCF) aged 2 years and older who have at least one non-Class I mutation in the cystic fibrosis transmembrane conductance regulator ( Methods: PwCF with two Class I variants who received ETI for an individual 4-6 week trial were identified within the real-world French compassionate programme and their response to ETI, as assessed by a centralized adjudication committee, was evaluated based on evolution of clinical data, lung function and sweat chloride. The lists of Class I Findings: Among 652 participants who were recruited in the French compassionate programme from May 19, 2022, to March 26, 2025, 163 had two Class I variants and received ETI. 155 (95%) were considered as non-responders and stopped ETI, whereas 8 (5%) were considered as responders and continued ETI. The six Class I variants probably responsive to ETI were: E831X and 4374+1G > A (each present in 2 participants), 1716+2T > C, 4382delA, 875+1G > A and CFTRdup1-3 (each present in 1 participant). Using CFTR2 and Interpretation: Class I variants are usually not responsive to ETI and pwCF with two true Class I variants should not be treated with ETI. However, exceptional Class I Funding: Association Vaincre la Mucoviscidose, Société Française de la Mucoviscidose, Filière Maladies Rares MUCO-CFTR.