A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-121/Tezacaftor/Deutivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 1 Through 11 Years of Age (VX21-121-105)

doi:10.1016/s2213-2600(26)00257-2

TIMBERLINE

Patient / Population Intervention / Exposition Vergleich Endpunkt

In 67 children aged 2 to 5 years with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor, a switch to once-daily vanzacaftor/tezacaftor/deutivacaftor was well tolerated and further reduced sweat chloride at 24 weeks.

N

67Patienten

Design

Phase 3, multicentre, open-label, single-arm study (protocol VX21-121-105, NCT05422222); children aged 2 to 5 years with an elexacaftor/tezacaftor/ivacaftor-responsive genotype took once-daily vanzacaftor/tezacaftor/deutivacaftor for 24 weeks, after either a stable regimen of elexacaftor/tezacaftor/ivacaftor for at least 28 days or a 4-week run-in on it. The same protocol ran cohorts aged 6 to 11 years, published as RIDGELINE, and 1 to under 2 years

Endpunkt

Safety and tolerability by adverse events; secondary the absolute change in sweat chloride and the proportion of children below 60 mmol/L and below 30 mmol/L

Relevanz

3Ergänzend — Kontext, kein Muss-Wissen.

ErgebnisAll 67 children completed the 24 weeks, with a mean exposure of 24.0 weeks. Adverse events occurred in 64 (95.5%), mostly mild (52.2%) or moderate (38.8%); two children (3.0%) had serious adverse events, neither considered related to the drug, and none stopped for an adverse event. Sweat chloride fell by a mean of 9.6 mmol/L (95% CI -12.1 to -7.0) from the elexacaftor/tezacaftor/ivacaftor baseline to a mean of 28.9 mmol/L at week 24; 92.4% of the children reached below 60 mmol/L and 65.2% below 30 mmol/L.

Rayment JH, Davies G, Gaffin JM, et al. The Lancet Respiratory Medicine. 2026. 10.1016/s2213-2600(26)00257-2

Diskussion & Kritik

The next triple combination reaches preschool children, and in 67 of them it was tolerated the way it was in the older cohorts, with two unrelated serious events and no withdrawals. The gain in CFTR function is real but modest in absolute terms, 9.6 mmol/L of sweat chloride on top of a regimen that already works, and two thirds of the children ended below the 30 mmol/L that marks near-normal channel function. Single-arm and open-label against each child's own baseline, so the comparison is with elexacaftor/tezacaftor/ivacaftor rather than with nothing, and 24 weeks says little about a drug these children would take for decades. What it buys is once-daily dosing and a label that reaches down to age two.