CFTR modulator therapy has transformed cystic fibrosis (CF) from a fatal childhood disease into an increasingly manageable chronic condition for most patients. The triple combination elexacaftor-tezacaftor-ivacaftor (Trikafta) produces large improvements in lung function and steep reductions in exacerbations for the roughly 90% of patients with at least one F508del allele, and its use has expanded to younger children and additional responsive mutations. The newest advance is vanzacaftor-tezacaftor-deutivacaftor (Alyftrek), a next-generation once-daily modulator approved in December 2024, which matched Trikafta on lung function while achieving lower sweat chloride (a marker of CFTR function) and covering additional mutations.
Symptomatic therapies remain important — dornase alfa and hypertonic saline for mucus clearance, azithromycin for its anti-inflammatory effect, and inhaled antibiotics for chronic infection. The key remaining unmet need is the roughly 10% of patients whose mutations are not amenable to modulators, for whom gene therapy, mRNA therapy, and gene editing are in active development.
Further reading: elexacaftor-tezacaftor-ivacaftor (Middleton et al., NEJM 2019; Barry et al., NEJM 2021); CF review (Ong & Ramsey, JAMA 2023); vanzacaftor-tezacaftor-deutivacaftor (Alyftrek) 2024 approval.