CFTR modulator therapy: transforming the landscape of clinical care in cystic fibrosis

Abstract

Following discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 and subsequent elucidation of the varied CFTR protein abnormalities that result, a new era of cystic fibrosis management has emerged-one in which scientific principles translated from the bench to the bedside have enabled us to potentially treat the basic defect in the majority of children and adults with cystic fibrosis, with a resultant burgeoning adult cystic fibrosis population. However, the long-term effects of these therapies on the multiple manifestations of cystic fibrosis are still under investigation. Understanding the effects of modulators in populations excluded from clinical trials is also crucial. Furthermore, establishing appropriate disease measures to assess efficacy in the youngest potential trial participants and in those whose post-modulator lung function is in the typical range for people without chronic lung disease is essential for continued drug development. Finally, recognising that a health outcome gap has been created for some people and widened for others who are not eligible for, cannot tolerate, or do not have access to modulators is important.; Competing Interests: Declaration of interests In the last 36 months, unrelated to this work, JLT-C has received grants to her institution from the Cystic Fibrosis Foundation (CFF), the National Institutes of Health, Vertex Pharmaceuticals, Eloxx, and 4DMT; she has received fees from Vertex Pharmaceuticals related to consultation on clinical research design, participation on advisory boards, and speaking engagements; and has served on advisory boards or provided clinical trial design consultation for Insmed, 4DMT, and AbbVie. JLT-C has served as chair of a data monitoring committee for AbbVie. She serves as the adult patient care representative to the CFF board of trustees, and on the CFF's clinical research executive committee, clinical research advisory board, as immediate past chair of the Cystic Fibrosis Therapeutics Development Network's Sexual Health, Reproduction and Gender Research working group, and as co-chair of the Heath Equity Team Science Awards study section. She also serves on the scientific advisory board for Emily's Entourage, on the American Thoracis Society Respiratory Health Awards Working Group, and as chair-elect of the International Conference Committee. She is an associate editor for the Journal of Cystic Fibrosis and a member of the international advisory board for The Lancet Respiratory Medicine. She serves on the Clinical Trials Review (CTLR) Study section for the National Institutes of Health National Heart, Lung, and Blood Institute. PDR reports that his previous institution, The Children's Hospital at Westmead, Sydney, has received remuneration for services provided by the Australian Central Over-Reading Centre he established for pharmaceutical-sponsored and investigator-led studies in cystic fibrosis. This renumeration will also be the case for his current institution (the University of Queensland) moving forward. MS has received grants and research support from: GSK, Insmed, Novartis, Trudell Pharma, Tel Aviv League for Lung Diseases; consultation fees from AstraZeneca, Boehringer Ingelheim, Dexcel, GSK, Kamada, Syncrony Medical, Trumed, Zambon; and speaker's fees from AstraZeneca, Boeringer Ingelheim, GSK, Kamada, Novartis, PhysioAssist, Sanofi, and Teva. MS serves as a data and safety monitoring board member for Bonus Biotherapeutics. MS is a member of management board of EMBARC, a member of the executive committee of the Israel Society for TB and Mycobacterial Diseases, an associate editor for the American Journal of Respiratory and Critical Care Medicine, and an editorial board member for the European Respiratory Journal and Chest. DGD reports grants from Chiesi Farmaceutici, the CF Trust, and the CFF to his institution. He reports consulting fees from Vertex and Insmed; and payments from Chiesi and Gilead for presentations. DGD receives support from the European Cystic Fibrosis Society and CFF for travel to mee ings. He participates on a data and safety monitoring board for the Nomab trial and CSL Behring. He serves on the research oversight scientific board for the UK Clinical Trials Accelerator Platform and is the Director of the European Cystic Fibrosis Society Clinical Trials Network. (Copyright © 2023 Elsevier Ltd. All rights reserved.)