The European Medicines Agency’s review of elexacaftor/tezacaftor/ivacaftor - extending its use to all people with cystic fibrosis aged 2 years and older who do not have two class I CFTR variants - editorial viewpoint

Sep 30, 2026

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Editorial viewpoint summarising a recent European Medicines Agency (EMA) evaluation of elexacaftor/tezacaftor/ivacaftor (ETI) and explaining how new regulatory approval expanded use beyond the original indication. The work frames cystic fibrosis as a life-shortening autosomal recessive disease driven by CFTR variants, reviews variant classes and existing EU modulator authorisations, and details EMA’s benefit–risk assessment based on in vitro data, controlled trials, and real-world evidence supporting broader patient eligibility.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Introduction

CFTR variants and existing modulators

Regulatory application and EMA/CHMP evaluation

Benefit–risk evaluation

Evidence base: in vitro, clinical, and real-world data

EUROPEAN RESPIRATORY JOURNAL EDITORIAL C. DRAI ET AL. The European Medicines Agency’s review of elexacaftor/ tezacaftor/ivacaftor: extending its use to all people with cystic fibrosis aged 2 years and older who do not have two class ICFTR variants Catherine Drai 1, Hanneke J. van der Woude2, Anne J. Lexmond 2, Tineke van den Hoorn 2, Peter G. M. Mol 2,3, Finbarr P. Leacy 4, Agnieszka Przybyszewska4, Bruno Sepodes 5 and Thomas Castelnovo1 1 European Medicines Agency, Amsterdam, The Netherlands. 2 Dutch Medicines Evaluation Board (MEB), Utrecht, The Netherlands. 3 Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. 4 Health Products Regulatory Authority, Dublin, Ireland. 5 Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal. Corresponding author: Catherine Drai (catherine.drai@ema.europa.eu) Shareable abstract (@ERSpublications) This viewpoint summarises the recent EMA evaluation of elexacaftor/tezacaftor/ivacaftor and how this new regulatory approval allowed use beyond the originally sought indication to all patients above 2 years of age eligible for CFTR modulators [https://bit.ly/3KoGPzI](https://bit.ly/3KoGPzI) Cite this article as: Drai C, van der Woude HJ, Lexmond AJ, et al. The European Medicines Agency’s review of elexacaftor/tezacaftor/ivacaftor: extending its use to all people with cystic fibrosis aged 2 years and older who do not have two class I CFTR variants. Eur Respir J 2026; 67: 2501506 [DOI: 10 . 1183/13993003 .01506-2025] . Copyright ©The authors 2026 This version is distributed under the terms of the Creative Commons Attribution NonCommercial Licence 4 .0. For commercial reproduction rights and permissions contact [permissions@ersnet.org](permissions@ersnet.org) Received: 18 July 2025 Accepted: 16 Sept 2025 Cystic fibrosis (CF) is a life-threatening, life-shortening, autosomal recessive disease caused by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes for a chloride ion channel protein present in apical cell membranes in many epithelial organs [1] . The disease affects approximately 56 000 individuals in Europe [2] and 160 000 people globally [3] . In the European Union (EU), CF is considered an orphan disease [4] . In people with CF, mutations in both copies of the CFTR gene result in protein absence or functional deficiencies. The resulting failure to regulate chloride transport can lead to the accumulation of mucus in the lungs, loss of exocrine pancreatic function, impaired intestinal absorption, reproductive dysfunction, and elevated sweat chloride concentration [5–7] . At present, more than 2000 CFTR gene variants have been identified [8] . Not all CFTR mutations cause CF and disease-causing variants are categorised according to the mechanisms by which they disrupt CFTR function. There are currently six (or even seven) defined classes: defective protein production (class I), defective protein processing (class II), defective regulation (class III), defective conductance (class IV), reduced amounts of functional CFTR protein (class V) and reduced membrane stability (class VI) [9, 10] . The F508del CFTR variant is the most frequent CF-causing variant; the non-F508del population of people with CF is genetically heterogeneous [11] . A number of CFTR modulator therapies have been authorised in the EU since 2012: Kalydeco (ivacaftor) for selected gating variants [12]; Orkambi (lumacaftor/ivacaftor) for F508del homozygous variants [13]; and Symkevi (tezacaftor/ivacaftor) for F508del homozygous variants or one of 14 residual function variants clinically shown to be responsive to therapy together with an F508del variant [14] . Introduction [https://doi.org/10.1183/13993003.01506-2025](https://doi.org/10.1183/13993003.01506-2025) Eur Respir J 2026; 67: 2501506 Kaftrio (consisting of the CFTR correctors elexacaftor and tezacaftor toget

FAQs

What does the editorial viewpoint summarise about EMA’s ETI review?

It summarises the EMA evaluation of elexacaftor/tezacaftor/ivacaftor and explains how regulatory approval allowed use beyond the originally sought indication.

Which patient group does the extended ETI use target?

The extended approval covers people with cystic fibrosis aged 2 years and older who do not have two class I CFTR variants, as described in the title and abstract.

What types of evidence were included in EMA’s benefit–risk evaluation?

The submission included in vitro FRT data for responsive variants, a randomised controlled study with an open-label extension, and a prospective observational real-world study supporting efficacy in people without a F508del mutation.

Sep 30, 2026

Uploaded by Bulrr