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Publications

Journal Article Epublish

PubMed: 42935985 DOI: 10.1183/23120541.00214-2026

Long-term safety and efficacy of lumacaftor/ivacaftor in children aged ≥12 months of age with cystic fibrosis: a 96-week open-label study.

ERJ Open Res 12(5)

Authors: Edith T Zemanick, Susanna A McColley, Rachel W Linnemann, Jonathan H Rayment, William T Harris, Bonnie Ramsey, Edward F McKone, Elizabeth Tullis, Marcus A Mall, Jennifer L Taylor-Cousar, Patrick R Sosnay, Neil Ahluwalia, Lingyun Liu, Mark Jennings, Margaret Rosenfeld

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.

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.

MeSH

Safety, Fibrosis, Aged, Drug-Related Side Effects And Adverse Reactions, Cystic Fibrosis, Therapeutics, Child