Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 5;61(5):2202437.
doi: 10.1183/13993003.02437-2022. Print 2023 May.

The French compassionate programme of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant

Pierre-Régis Burgel  1   2   3 , Isabelle Sermet-Gaudelus  3   4   5 , Isabelle Durieu  3   6   7 , Reem Kanaan  2   3 , Julie Macey  8 , Dominique Grenet  9 , Michele Porzio  10 , Nathalie Coolen-Allou  11 , Raphael Chiron  12 , Christophe Marguet  13 , Benoit Douvry  14 , Nadine Dufeu  15 , Isabelle Danner-Boucher  16 , Pierre Foucaud  17 , Lydie Lemonnier  17 , Emmanuelle Girodon  18 , Jennifer Da Silva  2   3 , Clémence Martin  19   2   3 ; French CF Reference Network study group; Claire Andrejak, Pascaline Priou, Bénédicte Richaud-Thiriez, Julie Macey, Sylvie Montcouquiol, Benoit Douvry, Natacha Remus, Annlyse Fanton, Nathalie Coolen-Allou, Elsa Gachelin, Constance Vuillard, Camille Audousset, Louise Duthoit, Elisabeth Bellet-Fraysse, Jeanne Languepin, Isabelle Durieu, Raphaele Nove-Josserand, Camille Ohlmann, Quitterie Raynaud, Nadine Dufeu, Raphael Chiron, Yves Billon, Isabelle Danner-Boucher, Adrien Tissot, Sylvie Leroy, Frédérique Aubourg, Espérie Burnet, Pierre-Régis Burgel, Nicolas Carlier, Jennifer Da Silva, Isabelle Fajac, Emmanuelle Girodon, Reem Kanaan, Isabelle Honoré, Clémence Martin, Muriel Le Bourgeois, Isabelle Sermet-Gaudelus, Laurence Le Clainche-Viala, Harriet Corvol, Clémence Dehillotte, Pierre Foucaud, Lydie Lemonnier, Graziella Brinchault, Bruno Ravoninjatovo, Jean Le Bihan, Sophie Ramel, Christophe Marguet, Michele Porzio, Laurence Weiss, Dominique Grenet, Sandra de Miranda, Laure Cosson, Julie Mankikian, Delphine Pouradier
Affiliations

The French compassionate programme of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant

Pierre-Régis Burgel et al. Eur Respir J. .

Abstract

Background: The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (CF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for people with CF carrying one of 177 rare variants.

Methods: An observational study was conducted to evaluate the effectiveness of ETI in people with CF with advanced lung disease who were not eligible for ETI in Europe. All patients with no F508del variant and advanced lung disease (defined as having a percent predicted forced expiratory volume (ppFEV1) <40% and/or being under evaluation for lung transplantation) and enrolled in the French compassionate programme initiated ETI at recommended doses. Effectiveness was evaluated by a centralised adjudication committee at 4-6 weeks in terms of clinical manifestations, sweat chloride concentration and ppFEV1.

Results: Among the first 84 people with CF included in the programme, ETI was effective in 45 (54%), and 39 (46%) were considered to be nonresponders. Among the responders, 22 (49%) out of 45 carried a CFTR variant that is not currently approved by the FDA for ETI eligibility. Important clinical benefits, including suspending the indication for lung transplantation, a significant decrease in sweat chloride concentration by a median (interquartile range (IQR)) -30 (-14--43) mmol·L-1 (n=42; p<0.0001) and an improvement in ppFEV1 by +10.0 (6.0-20.5) percentage points (n=44; p<0.0001), were observed in those for whom treatment was effective.

Conclusion: Clinical benefits were observed in a large subset of people with CF with advanced lung disease and CFTR variants not currently approved for ETI.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: P-R. Burgel reports support for the present work from Vaincre la Mucoviscidose. P-R. Burgel reports grants from Boehringer Ingelheim, GSK, Vertex; consulting fees and lecture honoraria from Boehringer Ingelheim, GSK, AstraZeneca, Vertex, Chiesi, Pfizer, Novartis, Zambon, Insmed; outside the submitted work. I. Sermet-Gaudelus reports support from the present manuscript from French CF association for primary nasal cell generation and Institut Necker Enfants Malades. I. Sermet-Gaudelus reports grants from Institut Necker Enfants Malades; is a member of scientific advisory board and received an innovation award from Vertex; travel support from North American Cystic Fibrosis Conference, Société Francais de Mucoviscidose; outside the submitted work. C. Marguet reports payment for expert testimony from Vertex; travel support from Sanofi; advisory board participation with Vertex, Zambon, Viatris, Sanofi; leadership role with French Paediatric Pulmonology and Allergy Society; outside the submitted work. B. Douvry reports grants and payment for expert testimony from Vertex, outside the submitted work. C. Martin reports lecture honoraria from AstraZeneca, Chiesi, Zambon; travel support from Zambon, Sanofi; advisory board membership from Vertex, Zambon, GSK; outside the submitted work. All other authors have nothing to disclose.

Comment in