Long-term safety and efficacy of lumacaftor/ivacaftor in children aged ≥12 months of age with cystic fibrosis: a 96-week open-label study
15 affiliations
- 1Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- 2Ann and Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- 3Emory University, Children's Healthcare of Atlanta, Atlanta, GA, USA
- 4British Columbia Children's Hospital, Vancouver, BC, Canada
- 5University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 6Seattle Children's Hospital, Seattle, WA, USA
- 7St Vincent's University Hospital, Dublin, Ireland
- 8St Michael's Hospital, Toronto, ON, Canada
- 9Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
- 10German Center for Lung Research (DZL), associated partner site Berlin, Berlin, Germany
- 11German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany
- 12Cluster of Excellence ImmunoPreCept, Charité – Universitätsmedizin Berlin, Berlin, Germany
- 13National Jewish Health, Denver, CO, USA
- 14Vertex Pharmaceuticals Incorporated, Boston, MA, USA
- 15Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, Seattle, WA, USA
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.
Methods: 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.
Results: 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.
Conclusions: 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.
Related
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BibTeX
@article{zemanick2026longterm,
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}},
author = {Edith T. Zemanick and Susanna A. McColley and Rachel W. Linnemann and Jonathan H. Rayment and William T. Harris and Bonnie Ramsey and Edward F. McKone and Elizabeth Tullis and Marcus A. Mall and Jennifer L. Taylor-Cousar and Patrick R. Sosnay and Neil Ahluwalia and Lingyun Liu and Mark Jennings and Margaret Rosenfeld},
journal = {ERJ Open Research},
year = {2026},
month = sep,
doi = {10.1183/23120541.00214-2026},
url = {https://doi.org/10.1183/23120541.00214-2026},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Long-term safety and efficacy of lumacaftor/ivacaftor in children aged ≥12 months of age with cystic fibrosis: a 96-week open-label study
AU - Edith T. Zemanick
AU - Susanna A. McColley
AU - Rachel W. Linnemann
AU - Jonathan H. Rayment
AU - William T. Harris
AU - Bonnie Ramsey
AU - Edward F. McKone
AU - Elizabeth Tullis
AU - Marcus A. Mall
AU - Jennifer L. Taylor-Cousar
AU - Patrick R. Sosnay
AU - Neil Ahluwalia
AU - Lingyun Liu
AU - Mark Jennings
AU - Margaret Rosenfeld
PY - 2026
DA - 2026/09/01
JO - ERJ Open Research
DO - 10.1183/23120541.00214-2026
UR - https://doi.org/10.1183/23120541.00214-2026
AB - 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. Methods: 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. Results: 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. Conclusions: 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.
SN - 2312-0541
ER -