Emerging pharmacotherapies in cystic fibrosis

Cystic fibrosis (CF) is an autosomal dominant chloride channelopathy caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that results clinically in a multisystem disorder. The major source of morbidity and mortality in CF is lung disease, which is characterized by recurrent cycles of inflammation and infection and progressive respiratory decline. Therapeutics have traditionally focused on the downstream effects of the primary genetic defect. However, recent advances have shifted attention to modulation of upstream pathways and the defective CFTR protein itself. Areas covered: This review focuses on emerging pharmacotherapeutics for CF lung disease, with an emphasis on the evidence for CFTR modulators and a summary of emerging modulator therapies currently in phase II and III clinical trials as of July 2018. Results of relevant trials reported in peer-reviewed journals, scientific conference abstracts, and sponsor press releases are included. This manuscript also discusses new and upcoming advances in anti-inflammatory therapy, anti-infectives, mucolytics, and gene editing. Expert commentary: The therapeutic landscape in CF has changed dramatically in recent years, with significant benefits for patients. Cure is now a realistic target in those with specific mutations who commence CFTR-directed therapy prior to the onset of significant airways disease.