Cystic fibrosis

Benefits of cystic fibrosis combination therapies maintained in the long-term: trials

Tuesday, 23 Feb 2021


Treatment with lumacaftor-ivacaftor (Orkambi) was tolerated well and maintained its efficacy in children aged 6-11 years out to 120 weeks, according to long-term trial data.

Previous trials have demonstrated success with the combination therapy in children homozygous for the F508del-CFTR mutation out to 24 weeks. “The safety and efficacy of the lumacaftor-ivacaftor combination has not been evaluated in studies longer than 24 weeks in children aged 6-11 years at commencement of therapy,” wrote authors led by Dr Mark Chilvers, of the BC Children’s Hospital in Vancouver, in The Lancet Respiratory Medicine.

The new study was an extension of two earlier phase III trials; participants in those earlier studies were given the opportunity to enroll in the new VX15-809-110 trial, given substantial overlap in the previous studies’ protocols.

The new trial included a total of 239 children who were homozygous for the F508del-CFTR mutation, spread across sites in the UK, Australia, the US, and six other countries. Of those, 215 patients (90%) completed 96 weeks of treatment with lumacaftor-ivacaftor.

Most of the children experienced at least one adverse event, but the majority of these were considered mild (21%) or moderate (62%) in severity. The most common AEs included cough (65%), infective pulmonary exacerbation of CF (49%), and pyrexia (30%). A total of 72 patients experienced a serious AE (30%), with infection pulmonary exacerbations as the most common such events (21%).

Nine of the children (4%) discontinued treatment due to adverse events. There were no deaths in the trial.

The main measure of the treatment’s efficacy was decrease in lung clearance index 2.5% (LCI2.5). The improvements seen in this measure in the parent studies were generally maintained in the extension trial. The same was true for improvements in sweat chloride concentration, with improvements sustained for the longer follow-up period, and there were clinically significant improvements from parent study baseline with regard to CFQ-R respiratory domain scores.

Body-mass index also increased throughout the extension study, and other efficacy endpoints either remained stable or improved with lumacaftor-ivacaftor treatment.

The authors did note that as this trial was a voluntary extension study, there could be bias due to self-selection, though almost all eligible children did participate.

“These data support the long-term use of lumacaftor-ivacaftor in treating the underlying cause of cystic fibrosis in children aged 6 years or older homozygous for the F508del-CFTR mutation,” the authors concluded.

Long-term data on CF treatments is accumulating, with another study also published in The Lancet Respiratory Medicine focused on the tezacaftor-ivacaftor combination (Symkevi) in patients 12 years or older who were homozygous or heterozygous for the Phe508del CFTR mutation. In that trial, the combination was again well tolerated and effective for up to 120 weeks, supporting long-term use of the therapy.

Disclosures: Both studies mentioned were funded by Vertex Pharmaceuticals, which manufactures Orkambi and Symkevi, and several authors were employees of the company or had received financial support in the form of grants or personal fees.

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