Pulmonary Exacerbations and Cystic Fibrosis

Greg Duncan, CEO of Celtaxsys discussed cystic fibrosis (CF) and the role of pulmonary exacerbations. Celtaxsys recently announced top line results of its Phase 2 EMPIRE-CF trial evaluating oral, once daily anti-inflammatory molecule, acebilustat, for the treatment of cystic fibrosis (CF), irrespective of the causative genotype.

In the 200 patient, double-blind, placebo controlled study, acebilustat demonstrated clinically meaningful improvements in pulmonary exacerbations, both reducing the frequency of pulmonary exacerbations (PEx) and increasing time to next exacerbation over 48 weeks of therapy. Full results from the trial will be presented this fall at the North American Cystic Fibrosis Foundation annual meeting. CF is caused by the mutation of the CF transmembrane conductance regulator (CFTR) gene, causing the body to produce unusually thick mucus that clogs small airways leading to persistent lung inflammation and increasing risk of lung infections. The result of lung inflammation is permanent degradation of lung function over time. Lung disease remains the major cause of hospitalizations and premature death in CF.

CF lung inflammation is driven by immune system cells called neutrophils. The lungs of CF patients are flooded by excessive amounts of neutrophils, which upon entering the lungs release their DNA out into the airways. The neutrophils and their DNA add onto the thick and sticky mucus, further restricting the flow of air through the small airways. This is important because small airways are the channels through which air from outside the lung must pass in order to get to the final cul-de-sacs (alveoli) where oxygen is absorbed into the blood. The result is that not enough oxygen is absorbed in the lungs of CF patients.

In addition to releasing their DNA into the lung, neutrophils also release an enzyme called elastase (NE). In a healthy lung, elastase is a tool that neutrophils use to help them clear away debris and kill bacteria. Excessive amounts of elastase in the lungs of a CF patient begin to erode the very processes that neutrophils are intended to protect.