Cystic fibrosis · CFTR modulators
Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele
| Design | Phase 3, randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Elexacaftor with tezacaftor and ivacaftor |
| Control | Placebo |
| Population | 403 patients with cystic fibrosis and Phe508del-minimal function genotypes |
| Follow-up | 24 weeks |
| Primary endpoint | Absolute change from baseline in percentage predicted FEV1 at 4 weeks |
| Result | Percentage predicted FEV1 was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks than placebo. Pulmonary exacerbation rate was 63% lower. Cystic Fibrosis Questionnaire-Revised respiratory domain score and sweat chloride both improved substantially. |
| Secondary endpoints | Pulmonary exacerbation rate, CFQ-R respiratory domain, sweat chloride, body-mass index |
Elexacaftor-tezacaftor-ivacaftor was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective.
The trial authors, in the published abstract
The trial that changed cystic fibrosis from a disease of median survival in the thirties to something else entirely. It extended the STRIVE result from 4% of patients to roughly 90%, and it is why the field's subsequent questions are about de-escalating older therapies (SIMPLIFY) rather than adding new ones.
Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med 2019 Nov 7;381(19):1809-1819.