{ "abstract": "Aims: We evaluated long-term safety and efficacy of lumacaftor (LUM)/ivacaftor (IVA) in children aged 12 to <24 months with cystic fibrosis (CF) homozygous for F508del.\n\nMethods: This international, 96-week, phase 3, open-label study enrolled children who completed parent study 809-122 (after 2-week washout) or were LUM/IVA-naïve. The primary end-point was safety and tolerability. The secondary efficacy end-point was change from baseline in sweat chloride concentration.\n\nResults: 52 children (39 from 809-122; 13 LUM/IVA-naïve) participated. Mean±sd exposure to LUM/IVA was 597±162 days. All children had at least one adverse event, which were mostly mild (32.7%) or moderate (55.8%) in severity and consistent with common manifestations of CF or early childhood illnesses. One child (1.9%) discontinued study drug due to a treatment-emergent adverse event of increased alanine/aspartate aminotransferases that resolved after discontinuation. 12 (23.1%) children had serious adverse events, none of which was considered related to LUM/IVA. At week 96, mean absolute change from pre-treatment baseline in sweat chloride concentration was −21.0 (95% CI −27.6 to −14.3) mmol·L−1. Growth parameters, which did not change significantly, were in the normal range throughout the 96-week treatment period. Improvements from baseline were observed in mean fecal elastase-1, fecal calprotectin, and serum immunoreactive trypsinogen.\n\nConclusions: LUM/IVA remained generally safe and well-tolerated over 96 weeks. Improvements in sweat chloride concentration and markers of pancreatic function and intestinal inflammation were consistent with the parent study. These results demonstrate the long-term safety and efficacy of LUM/IVA in the 12 to 24-month-old population.", "abstract_shown": true, "affiliations": [ "Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA", "Ann and Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA", "Emory University, Children's Healthcare of Atlanta, Atlanta, GA, USA", "British Columbia Children's Hospital, Vancouver, BC, Canada", "University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA", "Seattle Children's Hospital, Seattle, WA, USA", "St Vincent's University Hospital, Dublin, Ireland", "St Michael's Hospital, Toronto, ON, Canada", "Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany", "German Center for Lung Research (DZL), associated partner site Berlin, Berlin, Germany", "German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany", "Cluster of Excellence ImmunoPreCept, Charité – Universitätsmedizin Berlin, Berlin, Germany", "National Jewish Health, Denver, CO, USA", "Vertex Pharmaceuticals Incorporated, Boston, MA, USA", "Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, Seattle, WA, USA" ], "article_type": "research article", "arxiv": null, "author_total": 15, "authors": [ { "affs": [ 0 ], "name": "Edith T. Zemanick" }, { "affs": [ 1 ], "name": "Susanna A. McColley", "orcid": "0000-0003-0842-728X" }, { "affs": [ 2 ], "name": "Rachel W. Linnemann", "orcid": "0000-0002-6839-0936" }, { "affs": [ 3 ], "name": "Jonathan H. Rayment", "orcid": "0000-0003-4955-8876" }, { "affs": [ 4 ], "name": "William T. Harris" }, { "affs": [ 5 ], "name": "Bonnie Ramsey" }, { "affs": [ 6 ], "name": "Edward F. McKone" }, { "affs": [ 7 ], "name": "Elizabeth Tullis" }, { "affs": [ 8, 9, 10, 11 ], "name": "Marcus A. Mall", "orcid": "0000-0002-4057-2199" }, { "affs": [ 12 ], "name": "Jennifer L. Taylor-Cousar", "orcid": "0000-0002-5436-9722" }, { "affs": [ 13 ], "name": "Patrick R. Sosnay" }, { "affs": [ 13 ], "name": "Neil Ahluwalia" }, { "affs": [ 13 ], "name": "Lingyun Liu" }, { "affs": [ 13 ], "name": "Mark Jennings" }, { "affs": [ 14 ], "name": "Margaret Rosenfeld" } ], "bibtex": "https://research.draconitic.com/paper/c3vt7bmvmrbpn.bib", "cited_by": 0, "doi": "10.1183/23120541.00214-2026", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13699409/", "id": "c3vt7bmvmrbpn", "issns": [ "2312-0541" ], "landing_url": "https://doi.org/10.1183/23120541.00214-2026", "language": "en", "licence": "CC-BY-NC-4.0", "licence_label": "CC BY-NC 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "14" ], [ "heading", "3" ], [ "heading", "9" ], [ "heading", "Cystic Fibrosis" ], [ "heading", "Original Research Article" ], [ "openalex", "2740|Cystic Fibrosis Research Advances" ] ], "openalex": "W7167843071", "pdf_url": "https://europepmc.org/articles/PMC13699409?pdf=render", "pmcid": "PMC13699409", "pmid": "42935985", "published": "2026-09-01", "publisher": "European Respiratory Society", "ris": "https://research.draconitic.com/paper/c3vt7bmvmrbpn.ris", "sources": [ { "first_seen": "2026-10-30T12:20:01Z", "native_id": "PMC13699409", "source": "pmc", "url": "https://doi.org/10.1183/23120541.00214-2026" }, { "first_seen": "2026-10-30T12:22:24Z", "native_id": "MED:42935985", "source": "europepmc", "url": "https://europepmc.org/article/MED/42935985" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2740|Cystic Fibrosis Research Advances", "subfield": "general" } ], "title": "Long-term safety and efficacy of lumacaftor/ivacaftor in children aged ≥12 months of age with cystic fibrosis: a 96-week open-label study", "title_text": "Long-term safety and efficacy of lumacaftor/ivacaftor in children aged ≥12 months of age with cystic fibrosis: a 96-week open-label study", "type": "peer-reviewed", "updated_at": "2026-10-30T12:35:59Z", "url": "https://research.draconitic.com/paper/c3vt7bmvmrbpn", "venue": "ERJ Open Research", "versions": [] }