Background
Elexacaftor–tezacaftor–ivacaftor, a combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, has been approved in Europe and the US for treating cystic fibrosis in patients with at least one F508del CFTR variant and certain rare variants, respectively. This study aimed to assess the clinical response to this treatment in cystic fibrosis patients without the F508del variant in France and to determine the responsiveness of CFTR variants to the treatment based on observed clinical responses.
Methods
The French compassionate program expanded access to elexacaftor–tezacaftor–ivacaftor for cystic fibrosis patients aged 6 years and older without the F508del variant, excluding those with two variants previously characterized as non-responsive. Participants underwent a 4–6 week trial of the treatment, with response determined by a centralized committee based on clinical data, lung function, and sweat chloride concentration changes.
Findings
By March 8, 2024, 516 patients were identified for inclusion, with 479 receiving the treatment. Among those without prior CFTR modulator treatment, 83 had at least one FDA-approved variant, with 81 (98%) responding positively. In responders, significant improvements in sweat chloride concentration and lung function were observed. Additionally, 177 out of 360 participants without FDA-approved variants responded positively. The study also classified 64 out of 251 CFTR variants as responsive or possibly responsive to the treatment.
Interpretation
The findings suggest that elexacaftor–tezacaftor–ivacaftor is effective for more than half of the cystic fibrosis population without the F508del variant in France, including those with variants not approved by the FDA. The study underscores the need for further research to evaluate the long-term safety and effectiveness of the treatment in this population.
Funding
The study was funded by Association Vaincre la Mucoviscidose, Société Française de la Mucoviscidose, and Filière Maladies Rares MUCO-CFTR.
