Cystic fibrosis · CFTR modulators
Triple Therapy for Cystic Fibrosis Phe508del-Gating and Residual Function Genotypes
| Design | Phase 3, randomised, double-blind, active-controlled trial |
|---|---|
| Treatment | Elexacaftor with tezacaftor and ivacaftor |
| Control | Active control: previously available CFTR modulator therapy |
| Population | 258 patients with Phe508del-gating or Phe508del-residual function genotypes |
| Follow-up | 8 weeks |
| Primary endpoint | Absolute change from baseline in percentage predicted FEV1 |
| Result | Elexacaftor-tezacaftor-ivacaftor increased percentage predicted FEV1 by 3.7 percentage points relative to baseline compared with active control (95% CI 2.8 to 4.6). |
| Secondary endpoints | Sweat chloride, CFQ-R respiratory domain, safety |
Elexacaftor-tezacaftor-ivacaftor was efficacious and safe in patients with Phe508del-gating or Phe508del-residual function genotypes and conferred additional benefit relative to previous CFTR modulators.
The trial authors, in the published abstract
The comparison is against active therapy rather than placebo, which is why the effect looks small next to VX17-445-102's 14 points — these patients already had partial CFTR function. It completed the case for triple therapy across essentially every modulator-eligible genotype.
Barry PJ, Mall MA, Álvarez A, et al. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med 2021 Aug 26;385(9):815-825.