Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor
SKYLINE trial design and results
Design
Two randomised, double-blind, active-controlled, non-inferiority trials
Treatment
Once-daily vanzacaftor with tezacaftor and deutivacaftor
Control
Twice-daily elexacaftor with tezacaftor and ivacaftor
Population
398 participants in trial VX20-121-102 and a larger cohort in VX20-121-103; median age 31 years
Follow-up
52 weeks
Primary endpoint
Non-inferiority for absolute change in percentage predicted FEV1
Result
Vanzacaftor-tezacaftor-deutivacaftor was non-inferior to elexacaftor-tezacaftor-ivacaftor for percentage predicted FEV1, and was safe and well tolerated.
Secondary endpoints
Sweat chloride, CFQ-R respiratory domain, safety
Vanzacaftor-tezacaftor-deutivacaftor is non-inferior to elexacaftor-tezacaftor-ivacaftor in terms of FEV1 % predicted, and is safe and well tolerated. Once daily dosing with vanzacaftor-tezacaftor-deutivacaftor reduces treatment burden, potentially improving adherence, compared with the twice daily regimen of the current standard of care.
The trial authors, in the published abstract
How it has aged
Not a step up in efficacy but in convenience — the argument is adherence and treatment burden, which in a lifelong therapy is not a trivial one. Whether it displaces VX17-445-102 will turn on CFTR restoration and the range of variants covered rather than on FEV1.
Publications
Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials
Keating C, Yonker LM, Vermeulen F, et al. Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. Lancet Respir Med 2025 Mar;13(3):256-271.
Non-inferior to elexacaftor-tezacaftor-ivacaftor for percentage predicted FEV1