SOLAR: a non-interventional study of outcomes over the long term of people with cystic fibrosis aged 6 years and older treated with ELX-TEZ-IVA using data from the French CF registry

Introduction Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has demonstrated efficacy in people with Cystic Fibrosis (pwCF) aged ≥6 years with ≥1 F508del allele in clinical trials. This registry-based cohort study aimed to describe real-world use and outcomes up to 36 months post-treatment initiation among pwCF aged ≥6 years treated with ELX/TEZ/IVA in France. Methods Outcomes included percent predicted forced expiratory volume in 1 s (ppFEV 1 ), intravenous (IV) treated pulmonary exacerbations (PEx), hospitalizations, nutrition, lung transplantation, mortality and, among pwCF ≥18 years, quality of life (CFQ-R). All results are presented by population (≥12 years and 6–11 years). In the ≥12 years, a subgroup analysis of pwCF with advanced lung disease (ALD), defined as ppFEV 1 ,< 40% at baseline, is presented. Results The study included 553 pwCF aged 6–11 years, with a mean age of 8.8 ( sd : 1.9) years at baseline, ppFEV 1 of 91.3% ( sd : 17.6), and mean follow-up of 8.9 months. In addition, 3313 pwCF aged ≥12 years were included, with a mean age at baseline of 27.6 ( sd : 11.7) years, ppFEV 1 of 65.4% ( sd : 24.8), and mean follow-up of 21.2 months. In the cohort aged 6–11, ppFEV 1 improved by +9.6% (95%CI: 7.6, 11.6) at 12 months and IV treated PEx annual rate decreased from 0.15 (95%CI: 0.11, 0.18) to 0.02 (0.00, 0.04) after 0-to12-months post-ELX/TEZ/IVA initiation. Among pwCF ≥12 years ppFEV 1 improved post-ELX/TEZ/IVA initiation by +16.2% (95%CI: 15.6, 16.8) at 24 months. IV treated PEx annual rate decreased from 0.92 (95%CI: 0.88, 0.95) during baseline to 0.14 (95%CI: 0.12, 0.15) after 12-to-24-months post-ELX/TEZ/IVA initiation. Similar benefits to those in the ≥12 years population were observed in the ALD subgroup. Conclusion This study confirms the longer-term, transformational clinical benefit of ELX/TEZ/IVA in pwCF aged ≥6 years in a French population, demonstrating sustained improvements across multiple health outcomes, including in pwCF with ALD that were not part of the pivotal clinical trials.