Cystic fibrosis research: The only constant is change

In this volume of the Journal, two articles may appear to be unrelated yet are tied together because they present the challenges of a changing clinical trial landscape for people with cystic fibrosis (CF). The late 1980s ushered in a new era in the CF community. Research unraveled the mystery of the basic defect on a genetic, molecular, and cellular level opening the potential for the development of targeted therapies. This rapid expansion of basic and translational research led to the regulatory approval of the first cystic fibrosis transmembrane regulator (CFTR) modulator in 2012. As of 2023, approximately 90% of people in the U.S. with CF have mutations that qualify for highly effective modulator therapy (HEMT) [ [1] Cystic fibrosis foundation patient registry 2021 annual report data. Cystic Fibrosis Foundation, Bethesda, Md2022 Google Scholar ]. These new therapies have been truly life altering for most people with CF but create challenges in designing future placebo-controlled clinical trials. Willingness of people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor (ETI) to participate in randomized modulator and inhaled antimicrobial clinical trialsJournal of Cystic FibrosisVol. 22Issue 4PreviewBroad availability of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies targeting the primary CF defect has changed the healthcare landscape for most people with CF (pwCF) [1]. The most recent market entry, elexacaftor/tezacaftor/ivacaftor (ETI), has the potential to clinically benefit >90% of the United States CF population [2]. Full-Text PDF Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double‐blind, placebo‐controlled phase 1/2 clinical studyJournal of Cystic FibrosisVol. 22Issue 4PreviewTreatment of cystic fibrosis (CF) has markedly improved, especially with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators [1,2]. However, even the most broadly active CFTR modulator combinations are incapable of treating a segment of the population, estimated to encompass around 7% of non-Hispanic white individuals with CF [3,4] and a greater percentage of those who are of non-white racial or ethnic backgrounds [2]. For such patients and those that do not tolerate modulators, genetic therapies such as gene editing, delivery of the full CFTR gene, or messenger RNA (mRNA) therapies are of particular interest. Full-Text PDF