Lumacaftor-ivacaftor is generally safe and well tolerated for the long-term treatment of children with cystic fibrosis (CF) homozygous for the F508del-CFTR (cystic fibrosis transmembrane conductance regulator) mutation, according to the results of a  multicenter, phase 3, open-label, extension study ( Identifier: NCT03125395) published in Lancet Respiratory Medicine.1

In children aged 2 to 5 years with CF homozygous for the F508del-CFTR mutation, results from a previous phase 3 study demonstrated that lumacaftor-ivacaftor was generally safe and well tolerated over 24 weeks of treatment ( Identifier: NCT02797132).2 Researchers sought to assess the long-term safety of lumacaftor-ivacaftor in a rollover study in which children received weight-based and age-based doses of oral lumacaftor-ivacaftor for up to 96 weeks, equivalent to up to 120 weeks of treatment in total.1 A total of 47 (82%) of 57 participants completed 96 weeks of treatment, and most participants (98%) had at least 1 adverse event, most of which were mild or moderate in severity.

The most common adverse events were cough, nasal congestion, pyrexia, rhinorrhea, and vomiting. A total of 15 participants had at least 1 serious adverse event, which were consistent with underlying CF or common childhood illnesses. Respiratory adverse events occurred in 5 participants, none of which were serious or led to treatment discontinuation. Mild or moderate elevated aminotransferase concentrations occurred in 10 participants. Three participants discontinued treatment because of adverse events.

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No clinically significant abnormalities or changes were seen in electrocardiograms, vital signs, pulse oximetry, ophthalmologic examinations, or spirometry assessments. Improvements in secondary endpoints were generally maintained through 96 weeks, including changes in sweat chloride concentration, an increase in growth parameters and pancreatic function, and stable lung function relative to baseline.

The study authors concluded, “These findings support the use of lumacaftor-ivacaftor for up to 120 weeks in young children with cystic fibrosis aged 2 years and older homozygous for the F508del-CFTR mutation.”1

Disclosure: This research was supported by Vertex Pharmaceuticals Incorporated. Please see the original reference for a full list of disclosures.


1. Hoppe JE, Chilvers M, Ratjen F, et al. Long-term safety of lumacaftor–ivacaftor in children aged 2–5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study. Lancet Respir Med. Published online May 6, 2021. doi: 10.1016/S2213-2600(21)00069-2

2. McNamara JJ, McColley SA, Marigowda G, et al. Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study. Lancet Respir Med. 2019;7(4):325-335. doi: 10.1016/S2213-2600(18)30460-0