Cystic Fibrosis Drug Ivacaftor May Improve Growth Too

By Reuters Staff

February 01, 2017

NEW YORK (Reuters Health) - In prepubescent children with cystic fibrosis, targeting the biological defect in the CFTR protein with ivacaftor (Kalydeco) may improve growth outcomes in addition to lung function, according to post hoc data from two clinical trials.

The increasing life expectancy of patients with CF is "leading to clinical challenges not previously encountered in this patient population," the study team notes in their report online January 31st in Pediatrics.

CF is caused by mutations in CFTR gene that lead to deficient or defective CFTR protein and reduced anion transport. Ivacaftor is a CFTR potentiator shown to improve lung function in addition to weight and BMI in patients with CF and a G551D- CFTR. "However, studies have yet to report the effects of ivacaftor on linear growth in children with CF," Dr. Michael Stalvey of University of Alabama at Birmingham and colleagues point out.

They assessed growth outcome data in 35 CF patients from the GOAL observational study of ivacaftor treatment and 48 from the ivacaftor placebo-controlled, randomized ENVISION study. All 83 children were between six and 11 years old and had one copy of the G551D-CFTR mutation.

In GOAL, ivacaftor treatment was associated with significant increases in height and weight z scores from baseline to six months - increases of 0.1 (p<0.05) and 0.26 (p<0.0001), respectively. Height growth velocities also increased significantly from three to six months (2.10-cm/year increase; p<0.01).

Similarly, in ENVISION, ivacaftor treatment led to significant increases in height and weight z scores from baseline to 48 weeks (increases of 0.17 and 0.35, respectively, both p<0.001). Height and weight growth velocities from baseline to 48 weeks were also significantly higher with ivacaftor than with placebo (differences of 1.08 cm/year; p<0.05 and 3.11 kg/year; p<0.001, respectively).

Impaired growth is common in CF patients, "both manifesting and contributing to the reduced lung function," the researchers say. This poor growth may be mediated by CFTR protein.

"Our study presents the first evidence that correction of the abnormally functioning CFTR channel is associated with improved linear growth and supports the hypothesis that defective CFTR function directly contributes to impaired linear growth in CF," they write.

They caution that neither study was specifically designed or powered to address the association between ivacaftor and linear growth or growth velocities.

"We also recognize that these improvements are seen in conjunction with weight gain, as well as improved pulmonary function, which could confound the influence of CFTR on linear growth; nevertheless, the consistency of the data and the strength of preclinical data indicating a role for CFTR suggest that a CFTR-mediated pathway likely has at least some impact."

"Improving growth with CFTR potentiator therapy, either directly or indirectly, should be a goal of all CF health care providers, which reinforces the need for early initiation of CFTR restoration therapy when possible," the researchers conclude.

The study was supported in part by Vertex Pharmaceuticals, makers of ivacaftor. Several authors disclosed financial relationships with the company.


Pediatrics 2017.