Safety and efficacy of treatment with lumacaftor in combination with ivacaftor in younger patients with cystic fibrosis.
Expert Rev Respir Med. 2019 Mar 30;:
Authors: Cheng PC, Alexiou S, Rubenstein RC
INTRODUCTION: Cystic fibrosis (CF) is the most common autosomal recessive disorder affecting approximately 70,000 people worldwide. The lack of functional cystic fibrosis transmembrane conductance regulator (CFTR) causes dysregulation of epithelial fluid transport in the lungs, gastrointestinal tract, and sweat glands. Areas covered: The most common disease-causing CFTR mutation, F508del, is present in nearly 75% of those affected and results in a defective protein. Therapies to improve the function of this mutant protein have the promise to reduce morbidity and mortality in the majority of patients with CF. The combination of lumacaftor, which corrects the aberrant intracellular trafficking of F508del, and ivacaftor, which potentiates CFTR function, is known as OrkambiTM, and is the first drug approved for the treatment of cystic fibrosis (CF) in patients who are homozygous for F508del. OrkambiTM is currently approved for use in children aged 2 and older based on recent data from open-label Phase 3 clinical safety studies. In older patients, treatment with lumacaftor/ivacaftor is associated with a modest, statistically significant improvement in lung function and reduced pulmonary exacerbations in placebo-controlled trials; these findings are also observed in Phase IV observational studies. While severe side effects are rare, chest tightness, elevation of transaminases, and cataracts have been reported and recommendations for monitoring have been established. Expert opinion: OrkambiTM somewhat improves clinical outcomes for people with CF who are homozygous for the F508del mutation, and does so with a reasonable safety profile. This therapy represents a major advance in the therapy for CF, but further advances are needed, perhaps with addition of a third agent to this combination small molecule therapy, in order to expand both the targeted population and beneficial effects.
PMID: 30929526 [PubMed – as supplied by publisher]