Real-Life Experience With a Generic Formulation of Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis With Responding Variants

Pediatr Pulmonol. 2026 Jun;61(6):e71706. doi: 10.1002/ppul.71706.

Abstract

Introduction: Elexacaftor/Tezacaftor/Ivacaftor (ETI) has revolutionized cystic fibrosis (CF) care. In Argentina, the absence of patent restrictions allowed the production of a generic ETI formulation (ETIgf), significantly reducing costs.

Objective: This study evaluates the real-world clinical impact of ETIgf in people with CF (pwCF).

Methods: This prospective, single-center observational study in Buenos Aires, Argentina, included 71 pwCF (≥ 6 years) with responsive variants. Participants were categorized as: Group 1 (modulator-naïve) or Group 2 (previously on lumacaftor/ivacaftor). Clinical outcomes, including ppFEV1, LCI2.5, BMI z-score, CFQ-R, sweat chloride concentration (SCC), fecal elastase levels, liver enzymes and pulmonary exacerbations (PEx), were assessed over 12 months following the initiation of ETIgf.

Results: Group 1 included 43 patients, and Group 2 included 28 patients (median age: 10.9 and 10.6 years, respectively). The mean percentage change from baseline after 12 months of treatment for Group 1 and Group 2 was: ppFEV1 +20.8 (p < 0.01) and +18.5 (p < 0.01); LCI2.5 -13.3 (p < 0.01) and -11.2 (p < 0.05); CFQ-R + 66.1 (p < 0.01) and +30.4 (p < 0.01); and SCC -53.1 (p < 0.01) and -58.2 (p < 0.01), respectively. BMI z-score increased by 0.5 in Group 1 (p < 0.001), while Group 2 showed a non-significant increase. Pulmonary exacerbations were reduced by 95% in both groups. No changes were observed in fecal elastase levels. Adverse events were mild: five patients experienced elevated transaminase levels and three presented with a rash.

Conclusion: ETIgf demonstrates robust clinical efficacy and safety, mirroring results reported for the originator. These findings highlight the viability of affordable generic modulators in expanding global access to life-changing therapy.

Keywords: CFTR modulators; Elexacaftor/tezacaftor/ivacaftor; cystic fibrosis; real life.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Aminophenols* / therapeutic use
  • Argentina
  • Benzodioxoles* / therapeutic use
  • Child
  • Chloride Channel Agonists* / therapeutic use
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / physiopathology
  • Drug Combinations
  • Female
  • Humans
  • Indoles* / therapeutic use
  • Male
  • Prospective Studies
  • Pyrazoles
  • Pyridines* / therapeutic use
  • Pyrrolidines* / therapeutic use
  • Quinolines
  • Quinolones* / therapeutic use
  • Quinuclidines* / therapeutic use
  • Sweat / chemistry
  • Treatment Outcome

Substances

  • Benzodioxoles
  • Quinolones
  • Indoles
  • Drug Combinations
  • Aminophenols
  • elexacaftor, ivacaftor, tezacaftor drug combination
  • Pyrrolidines
  • Chloride Channel Agonists
  • Quinuclidines
  • Pyridines
  • Pyrazoles
  • Quinolines