[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-456294-105":59,"doc-detail-456294-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","advances-in-cystic-fibrosis-cftr-modulator-triple-combinations","Advances in cystic fibrosis - CFTR modulator triple combinations","","Triple combinations of CFTR modulators have transformed cystic fibrosis care by targeting the underlying CFTR protein defect. Initially designed for the F508del variant, these therapies are now effective across many CFTR genotypes, though not for every patient. The editorial outlines the historical evolution from symptomatic management to breakthrough oral modulators, explains potentiators and correctors, and summarizes development and first regulatory approvals in the USA and Europe.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/advances-in-cystic-fibrosis-cftr-modulator-triple-combinations/456294/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/advances-in-cystic-fibrosis-cftr-modulator-triple-combinations/456294.png","ImageObject",300,407,{"name":92,"@type":93},"Bulrr","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What makes CFTR modulator triple combinations a major advance in cystic fibrosis treatment?","Question",{"text":112,"@type":113},"They partially restore CFTR-dependent ion transport and address the underlying CFTR protein defect, extending beyond earlier variant-specific approaches.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do CFTR potentiators and correctors differ in their mechanisms?",{"text":117,"@type":113},"Potentiators increase CFTR channel opening, while correctors improve protein folding and trafficking to increase functional CFTR at the cell surface.",{"name":119,"@type":110,"acceptedAnswer":120},"Which triple combination therapies are discussed as first regulatory approvals in the USA and Europe?",{"text":121,"@type":113},"The editorial highlights elexacaftor/tezacaftor/ivacaftor (ETI) and vanzacaftor/tezacaftor/deutivacaftor (VTD), including their variant eligibility and approval timelines.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},456294,1790816424,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","EUROPEAN RESPIRATORY JOURNAL EDITORIAL  \nP-R. BURGEL AND M.A. MALL  \nAdvances in cystic fibrosis: CFTR modulator triple combinations  \nPierre-Régis Burgel 1,2,3 and Marcus A. Mall 3,4,5,6,7  \n1 Respiratory Medicine and Cystic Fibrosis National Reference Center, Hôpital Cochin, AP-HP Centre Université Paris Cité, Paris, France. 2 Institut Cochin, Inserm U1016, Université Paris Cité, Paris, France. 3 ERN-Lung CF Core Network, Frankfurt, Germany. 4 Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany. 5German Center for Lung Research (DZL), associated partner site Berlin, Berlin, Germany. 6German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany. 7Cluster of Excellence ImmunoPreCept, Charité – Universitätsmedizin Berlin, Berlin, Germany.  \nCorresponding author: Pierre-Régis Burgel ( [pierre-regis.burgel@aphp.fr](pierre-regis.burgel@aphp.fr))  \nShareable abstract (@ERSpublications)  \nTriple combinations of CFTR modulators have revolutionised the care of people with CF. Initially developed for the F508del variant, these drugs are effective in many other CFTR variants, making them suitable for most, but not all, people with CF. [https://bit.ly/49yHjha](https://bit.ly/49yHjha)  \nCite this article as: Burgel P-R, Mall MA. Advances in cystic fibrosis: CFTR modulator triple combinations. Eur Respir J 2026; 67: 2501783 [DOI: 10.1183/13993003.01783-2025] .  \nCopyright ©The authors 2026 .  \nThis version is distributed under the terms of the Creative Commons Attribution NonCommercial Licence 4 .0. For commercial reproduction rights and permissions contact [permissions@ersnet.org](permissions@ersnet.org)  \nReceived: 25 Aug 2025  \nAccepted: 22 Oct 2025  \nCystic fibrosis and the discovery of CFTR modulators  Cystic fibrosis (CF) is a autosomal recessive genetic disease caused by pathogenic variants in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein [1] . Defective CFTR protein reduces or abolishes CFTR-dependent chloride and bicarbonate transport in epithelia, leading to a multi-organ disease. In people with CF, lung disease is the main cause of death and involves a vicious circle with highly viscoelastic mucus, leading to mucus plugging, chronic inflammation and bacterial infection in the airways. These factors can lead to airway injury and bronchiectasis, and may progress to respiratory failure. For decades, advancements in CF care have primarily resulted from the refinement of symptomatic therapies such as airway clearance therapies, nutritional management, the use of inhaled and systemic antibiotics, and timely referrals for lung transplantation.  \nCFTR modulators are orally active small molecules that partially restore CFTR-dependent ion transport and have led to a breakthrough in the treatment of the underlying protein defect in CF. CFTR modulators have been available since 2012, initially only for the 4–5% of CF patients with the G551D gating variant [2], but it took several years to develop combinations effective for most people with CF. The introduction of the first triple CFTR modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), at the end of 2019 marked a significant advancement in the therapeutic approach to CF. ETI contains ivacaftor, a CFTR potentiator that increases CFTR channel opening at the apical membrane. Initially discovered based on high-throughput screening in G551D cells, it was subsequently demonstrated to restore CFTR function in additional gating variants. Elexacaftor and tezacaftor are CFTR correctors, which improve CFTR protein folding and trafficking, thereby increasing the number of functional proteins at the cell surface; they have been identified based on high throughput screening for their ability to restore chloride transport in F508del-expressing cells. CFTR potentiators and correctors act by binding to the misfolded CFTR protein, enhan","cbCaigYJALRdyHrc","https://ap.wps.com/l/cbCaigYJALRdyHrc","pdf",417880,"English","# Cystic fibrosis and the discovery of CFTR modulators\n## Role of defective CFTR in disease progression\n## Emergence of CFTR modulator therapy\n## Potentiators, correctors, and approved triple combinations\n## First regulatory approvals (USA and Europe)","[{\"question\":\"What makes CFTR modulator triple combinations a major advance in cystic fibrosis treatment?\",\"answer\":\"They partially restore CFTR-dependent ion transport and address the underlying CFTR protein defect, extending beyond earlier variant-specific approaches.\"},{\"question\":\"How do CFTR potentiators and correctors differ in their mechanisms?\",\"answer\":\"Potentiators increase CFTR channel opening, while correctors improve protein folding and trafficking to increase functional CFTR at the cell surface.\"},{\"question\":\"Which triple combination therapies are discussed as first regulatory approvals in the USA and Europe?\",\"answer\":\"The editorial highlights elexacaftor/tezacaftor/ivacaftor (ETI) and vanzacaftor/tezacaftor/deutivacaftor (VTD), including their variant eligibility and approval timelines.\"}]","Advances in cystic fibrosis - CFTR modulator triple combinations | PDF",1790745496,18]