Abstract
INTRODUCTION: Mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), a disease with life threatening pulmonary and gastrointestinal manifestations. Recent breakthrough therapies restore function to select disease-causing CFTR mutations. Ivacaftor is a small molecule that increases the open channel probability of certain CFTR mutations, producing clear evidence of bioactivity and efficacy in pediatric CF patients. CFTR modulators represent a significant advancement in CF treatment. Extending these therapies to young CF patients is proposed to have the greatest long term impact, potentially preventing later disease. AREAS COVERED: Here we summarize the research experience of CFTR modulators in pediatrics, focusing on ivacaftor and highlighting challenges in pediatric studies. As a result of these studies, ivacaftor has been approved in CF patients age 2 years and older who have one of ten CFTR mutations. EXPERT OPINION: Conducting studies in young CF patients presents unique challenges, including small numbers of patients and difficulty selecting sensitive biomarkers and meaningful outcome measures. Adverse events may be more pronounced in children and deserve special attention. Ongoing efforts must focus on expanding and validating new biomarkers, innovative study design, and thorough monitoring of adverse events in children treated with CFTR modulators.