Advancing cystic fibrosis treatment: investigational agents on the horizon.

Introduction: Cystic fibrosis (CF) treatment has been transformed by CF transmembrane conductance regulator (CFTR) modulator therapies, yet significant gaps remain for those with non-responsive or modestly responsive (below therapeutically relevant levels) genotypes and advanced disease. Emerging agents for genetic therapies and targeting symptoms are in development and offer hope for broader, more durable clinical benefits. This review synthesizes the latest clinical advances aiming to shape the future of CF care.

Areas covered: We examine investigational agents in clinical development, including: (1) alternative CFTR modulators (e.g., potentiators, correctors, and amplifiers); (2) gene-based therapies utilizing viral and non-viral vectors; (3) anti-inflammatory approaches; and (4) infection-targeted therapies. Clinical trial data and combination strategies are discussed.

Expert opinion: Despite dramatic improvements in clinical outcomes and survival in people with CF on modulator drugs, further efforts are warranted for ineligible/non-responsive individuals or intolerant to modulators. In addition, it remains vital to identify novel therapeutic strategies to mitigate lung damage and disease progression as infection and inflammation persist even in people with CF receiving 'highly effective' modulator therapy.