Tezacaftor, Ivacaftor Combination Generally Safe, Well Tolerated in Children With CF Under Age 12

Data from a phase 3 trial support the use of tezacaftor in combination with ivacaftor for the treatment of cystic fibrosis (CF) in children aged 6 to 11 years, finding that the treatment combination was generally safe and well tolerated.

Tezacaftor/ivacaftor has previously demonstrated safety and efficacy among patients aged 12 years and older who are homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation (F/F) or heterozygous for F508del-CFTR and a mutation associated with residual CFTR function (F/RF).

“In patients with CF harboring the F/F genotype and in many patients with F/RF genotypes, disease progression begins early in life; despite supportive care, CF is associated with impaired growth and decline in lung function over time,” wrote the researchers, adding that until now, the effect of tezacaftor/ivacaftor on CFTR has not been studied in children under the age of 12 years.

During the first half of the study, 13 children received either tezacaftor 50 mg once daily and ivacaftor 75 mg every 12 hours or tezacaftor 50 mg once daily and ivacaftor 150 mg every 12 hours, based on their weight, for 14 days. Throughout the treatment period, there were treatment-emergent related events (TEAEs) reported in 12 of the children, and all events were mild or moderate. TEAEs that occurred in at least 2 children included cough, headache, and nasal congestion.

There were no clinically meaningful findings related to the treatment combination observed in vital signs, electrocardiograms, results from serum chemistry, hematology, pulse oximetry, urinalysis, or physical examination.

For the second half of the study, 70 children received either tezacaftor 50 mg once daily and ivacaftor 75 mg every 12 hours or tezacaftor 100 mg once daily and ivacaftor 150 mg every 12 hours, based on their weight, for 24 weeks. A total of 67 patients completed their regimen.

Efficacy results revealed that tezacaftor/izacaftor reduced sweat chloride concentrations, indicating enhanced CFTR function. These reductions were rapid and sustained over the 24 weeks. At baseline, the children had relatively preserved lung function, which remained stable over the 24 weeks. The treatment combination also resulted in improvements in Cystic Fibrosis Questionnaire—Revised respiratory domain scores, indicating improved quality of life.

The majority (87.1%) of children in this part of the study had the F/F genotype, while 9 had F/RF genotypes. The most common TEAEs observed among this group were generally consistent with clinical manifestations of CF in children and the established safety profile of the treatment combination. They included: cough, pulmonary exacerbation of CF, pyrexia, nasal congestion, abdominal pain, rhinorrhea, and vomiting. Most of the TEAEs were mild or moderate, and there was 1 child who discontinued treatment for a serious adverse event of constipation.

“There was no evidence of an increased incidence of respiratory TEAEs associated with tezacaftor/ivacaftor treatment in this study, consistent with the results of tezacaftor/ivacaftor in patients aged >12 years,” wrote the researchers.

Reference:

Walker S, Flume P, McNamara J, et al. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis [published online June 25, 2019]. J Cyst Fibros. doi: 10.1016/j.jcf.2019.06.009.