Chest
Volume 143, Issue 1, January 2013, Pages 207-213
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Ahead of the Curve
Cystic Fibrosis Therapeutics: The Road Ahead

https://doi.org/10.1378/chest.12-1639Get rights and content

A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco.

Section snippets

What Lies Ahead

The pathophysiology of CF lung disease is known to involve self-perpetuating cycles of airway obstruction, infection, and inflammation,6 as illustrated at the bottom of Figure 1. Accordingly, many current and candidate treatments directly target one or more of these pathophysiologic elements; for example, there are multiple therapies currently addressing airway infections, inflammation, and airway mucus rheology. More encouraging are novel therapies, including CFTR modulators and airway cell

Conclusion

The past 20 years have transformed the field of CF treatment so that changing the course of this fatal illness is becoming a reality. The view of the road ahead has never been so encouraging in CF therapeutics, and there is cause for unprecedented optimism for anyone who cares for people with this devastating disease. In the next decade, it is likely that both a CFTR potentiator (Kalydeco) and at least one CFTR corrector may be available for the majority of patients with CF. These drugs have a

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Hoffman receives grant funding from the Cystic Fibrosis Foundation and the National Institutes of Health. Dr Ramsey, in her capacity as director of the Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, has received grants from the following companies in the past 3 years: AlgiPharma AS; Amgen, Inc; Aradigm Corporation; Axcan Pharma, Inc; Bayer Healthcare

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