A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)

Summary

The purpose of this study evaluates the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who were heterozygous for F508del and a minimal function mutation (F/MF participants).

Timeline

Start

2021-09-14

Primary completion

2023-05-12

Completion

2023-11-21

Outcome

Met primary endpoint

paper Vanzacaftor-tezacaftor-deutivacaftor is non-inferior to elexacaftor-tezacaftor-ivacaftor in terms of FEV1 % predicted, and is safe and well tolerated. PMID 39756424 ↗

registry analysis (non-inferiority test); ELX/TEZ/IVA vs VX-121/TEZ/D-IVA; p < 0.0001; LS Mean difference 0.2 (95% CI -0.7 to 1.1); Mixed Models Repeated Measures NCT05033080 ↗

Publications

• Keating C, Yonker LM, Vermeulen F, Prais D, Linnemann RW, Trimble A, Kotsimbos T, Mermis J, Braun AT, O'Carroll M, Sutharsan S, Ramsey B, Mall MA, Taylor-Cousar JL, McKone EF, Tullis E, Floreth T, Michelson P, Sosnay PR, Nair N, Zahigian R, Martin H, Ahluwalia N, Lam A, Horsley A; VX20-121-102 Study Group; VX20-121-103 Study Group. 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. doi: 10.1016/S2213-2600(24)00411-9. Epub 2025 Jan 2.
• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Ivacaftor	Other / unclassified	150 mg	Oral
Subject	Vanzacaftor	Small molecule	20 mg	Oral
Subject	deutivacaftor	Unknown	250 mg	Oral
Comparator	elexacaftor	Small molecule	200 mg	Oral
Subject	tezacaftor	Other / unclassified	100 mg	Oral

Indications