{
  "abstract": "RATIONALE: In an 8-week, active-controlled, phase 3 study (445-104), elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in participants ≥ 12 years of age with cystic fibrosis (CF) and F508del-gating (F/G) or F508del-residual function (F/RF) genotypes, conferring additional clinical benefits relative to IVA and TEZ/IVA. Participants who completed this 8-week parent study continued to an open-label extension. OBJECTIVE: To assess the long-term safety and efficacy of ELX/TEZ/IVA in adolescents and adults with CF and F/G or F/RF genotypes. METHODS: This 2-part (Part A [96 weeks] and Part B [48 weeks]) phase 3 open-label extension study enrolled adolescents and adults age ≥ 12 years with CF and F/G or F/RF genotypes who completed study 445-104. Primary endpoint (Part A and Part B) was safety and tolerability. Secondary endpoints (Part A only) included absolute changes in percent predicted FEV1 (ppFEV1), sweat chloride concentration, CF Questionnaire-Revised (CFQ-R) respiratory domain score, and body mass index (BMI). RESULTS: A total of 251 participants received ≥ 1 dose of ELX/TEZ/IVA in Part A; 217 (86.5%) completed treatment. In Part A, 96.0% of participants had ≥ 1 adverse event (AE), which for most were mild (32.3%) or moderate (55.0%) in severity. Thirteen participants (5.2%) discontinued due to treatment-emergent AEs. Participants who received ELX/TEZ/IVA in the parent study maintained improvements in ppFEV1, sweat chloride concentration, CFQ-R respiratory domain score, and BMI while participants who received IVA or TEZ/IVA (active controls) in parent study had similar improvements after transitioning to ELX/TEZ/IVA. Eighty-four participants (33.5%) entered Part B, 96.4% of whom discontinued due to commercial drug availability. In Part B, 62 participants (73.8%) had ≥ 1 AE, which for most were mild or moderate in severity and none of which led to discontinuation. CONCLUSIONS: ELX/TEZ/IVA remained generally safe and well-tolerated with no new safety findings. Improvements in lung function, CFTR function, respiratory symptoms, and nutritional status after starting ELX/TEZ/IVA were maintained through 96 weeks of follow-up. These results demonstrate the safety and durable efficacy of ELX/TEZ/IVA in adolescents and adults with F/G or F/RF genotypes.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 117,
  "authors": [
    {
      "name": "James Chmiel"
    },
    {
      "name": "Kimberly Mcbennett"
    },
    {
      "name": "Kimberly Mcbennett"
    },
    {
      "name": "Bradley Quon"
    },
    {
      "name": "Bradley Quon"
    },
    {
      "name": "Carla Colombo"
    },
    {
      "name": "Carla Colombo"
    },
    {
      "name": "Elke de Wachter"
    },
    {
      "name": "Elke de Wachter"
    },
    {
      "name": "Isabelle Fajac"
    },
    {
      "name": "Isabelle Fajac"
    },
    {
      "name": "Pedro Mondejar-Lopez"
    },
    {
      "name": "Deepika Polineni"
    },
    {
      "name": "Deepika Polineni"
    },
    {
      "name": "Philip Robinson"
    },
    {
      "name": "Sivagurunathan Sutharsan"
    },
    {
      "name": "Sivagurunathan Sutharsan"
    },
    {
      "name": "Marcus Mall"
    },
    {
      "name": "Edward Mckone"
    },
    {
      "name": "Edward Mckone"
    },
    {
      "name": "Bonnie Ramsey"
    },
    {
      "name": "Jennifer Taylor-Cousar"
    },
    {
      "name": "Jennifer Taylor-Cousar"
    },
    {
      "name": "Elizabeth Tullis"
    },
    {
      "name": "Elizabeth Tullis"
    },
    {
      "name": "Nina Suresh"
    },
    {
      "name": "Yaohua Zhang"
    },
    {
      "name": "Patrick Sosnay"
    },
    {
      "name": "Mark Jennings"
    },
    {
      "name": "Peter Barry"
    },
    {
      "name": "Peter Barry"
    },
    {
      "name": "Daniel Smith"
    },
    {
      "name": "Dominic Keating"
    },
    {
      "name": "Phil Robinson"
    },
    {
      "name": "Clements Barry"
    },
    {
      "name": "Lucy Burr"
    },
    {
      "name": "Claire Wainwright"
    },
    {
      "name": "Peter Middleton"
    },
    {
      "name": "Christiane Knoop"
    },
    {
      "name": "Eva van Braeckel"
    },
    {
      "name": "Francois Vermeulen"
    },
    {
      "name": "Winnie Leung"
    },
    {
      "name": "Larry Lands"
    },
    {
      "name": "Tacjana Pressler"
    },
    {
      "name": "Stephanie Bui"
    },
    {
      "name": "Oliver Le Rouzic"
    },
    {
      "name": "Nadine Dufeu"
    },
    {
      "name": "Isabelle Durieu"
    },
    {
      "name": "Isabelle Sermet-Gaudelus"
    },
    {
      "name": "Raphael Chiron"
    },
    {
      "name": "Mirjam Stahl"
    },
    {
      "name": "Alexander Kiefer"
    },
    {
      "name": "Lutz Naehrlich"
    },
    {
      "name": "Stephan Eisenmann"
    },
    {
      "name": "Rainald Fischer"
    },
    {
      "name": "Helge Hebestreit"
    },
    {
      "name": "Plant Barry"
    },
    {
      "name": "Noel Gerard Mcelvaney"
    },
    {
      "name": "Desmond Cox"
    },
    {
      "name": "Brian Casserly"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6w6cdgx1st7r8.bib",
  "cited_by": 0,
  "doi": "10.1093/annalsats/aaoag053",
  "fulltext_url": null,
  "id": "6w6cdgx1st7r8",
  "issns": [
    "2329-6933",
    "2325-6621"
  ],
  "landing_url": "https://hal.science/hal-05751982v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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    [
      "openalex",
      "2740|Cystic Fibrosis Research Advances"
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  "openalex": "W7136236822",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "41837895",
  "published": "2026-09-01",
  "publisher": "American Thoracic Society",
  "ris": "https://research.draconitic.com/paper/6w6cdgx1st7r8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "hal-05751982",
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  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
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      "origin": "hal:1.sdv.spee",
      "subfield": "epidemiology-public-health"
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  ],
  "title": "Safety and efficacy of elexacaftor/tezacaftor/ivacaftor in adolescents and adults with cystic fibrosis and F508del -gating and F508del -residual function genotypes: results from an open-label extension study",
  "title_text": "Safety and efficacy of elexacaftor/tezacaftor/ivacaftor in adolescents and adults with cystic fibrosis and F508del -gating and F508del -residual function genotypes: results from an open-label extension study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:35Z",
  "url": "https://research.draconitic.com/paper/6w6cdgx1st7r8",
  "venue": "Annals of the American Thoracic Society",
  "versions": []
}