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

@article{chmiel2026safety,
  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}},
  author = {James Chmiel and Kimberly Mcbennett and Kimberly Mcbennett and Bradley Quon and Bradley Quon and Carla Colombo and Carla Colombo and Elke de Wachter and Elke de Wachter and Isabelle Fajac and Isabelle Fajac and Pedro Mondejar-Lopez and Deepika Polineni and Deepika Polineni and Philip Robinson and Sivagurunathan Sutharsan and Sivagurunathan Sutharsan and Marcus Mall and Edward Mckone and Edward Mckone and Bonnie Ramsey and Jennifer Taylor-Cousar and Jennifer Taylor-Cousar and Elizabeth Tullis and Elizabeth Tullis and Nina Suresh and Yaohua Zhang and Patrick Sosnay and Mark Jennings and Peter Barry and Peter Barry and Daniel Smith and Dominic Keating and Phil Robinson and Clements Barry and Lucy Burr and Claire Wainwright and Peter Middleton and Christiane Knoop and Eva van Braeckel and Francois Vermeulen and Winnie Leung and Larry Lands and Tacjana Pressler and Stephanie Bui and Oliver Le Rouzic and Nadine Dufeu and Isabelle Durieu and Isabelle Sermet-Gaudelus and Raphael Chiron and Mirjam Stahl and Alexander Kiefer and Lutz Naehrlich and Stephan Eisenmann and Rainald Fischer and Helge Hebestreit and Plant Barry and Noel Gerard Mcelvaney and Desmond Cox and Brian Casserly},
  journal = {Annals of the American Thoracic Society},
  year = {2026},
  month = sep,
  doi = {10.1093/annalsats/aaoag053},
  url = {https://hal.science/hal-05751982v1},
  note = {CC BY-NC},
}

TY  - JOUR
TI  - 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
AU  - James Chmiel
AU  - Kimberly Mcbennett
AU  - Kimberly Mcbennett
AU  - Bradley Quon
AU  - Bradley Quon
AU  - Carla Colombo
AU  - Carla Colombo
AU  - Elke de Wachter
AU  - Elke de Wachter
AU  - Isabelle Fajac
AU  - Isabelle Fajac
AU  - Pedro Mondejar-Lopez
AU  - Deepika Polineni
AU  - Deepika Polineni
AU  - Philip Robinson
AU  - Sivagurunathan Sutharsan
AU  - Sivagurunathan Sutharsan
AU  - Marcus Mall
AU  - Edward Mckone
AU  - Edward Mckone
AU  - Bonnie Ramsey
AU  - Jennifer Taylor-Cousar
AU  - Jennifer Taylor-Cousar
AU  - Elizabeth Tullis
AU  - Elizabeth Tullis
AU  - Nina Suresh
AU  - Yaohua Zhang
AU  - Patrick Sosnay
AU  - Mark Jennings
AU  - Peter Barry
AU  - Peter Barry
AU  - Daniel Smith
AU  - Dominic Keating
AU  - Phil Robinson
AU  - Clements Barry
AU  - Lucy Burr
AU  - Claire Wainwright
AU  - Peter Middleton
AU  - Christiane Knoop
AU  - Eva van Braeckel
AU  - Francois Vermeulen
AU  - Winnie Leung
AU  - Larry Lands
AU  - Tacjana Pressler
AU  - Stephanie Bui
AU  - Oliver Le Rouzic
AU  - Nadine Dufeu
AU  - Isabelle Durieu
AU  - Isabelle Sermet-Gaudelus
AU  - Raphael Chiron
AU  - Mirjam Stahl
AU  - Alexander Kiefer
AU  - Lutz Naehrlich
AU  - Stephan Eisenmann
AU  - Rainald Fischer
AU  - Helge Hebestreit
AU  - Plant Barry
AU  - Noel Gerard Mcelvaney
AU  - Desmond Cox
AU  - Brian Casserly
PY  - 2026
DA  - 2026/09/01
JO  - Annals of the American Thoracic Society
DO  - 10.1093/annalsats/aaoag053
UR  - https://hal.science/hal-05751982v1
AB  - 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.
SN  - 2329-6933
SN  - 2325-6621
ER  -