Greg Duncan, President and Chief Executive Officer of Celtaxsys, provides an overview of cystic fibrosis (CF), an inherited chronic disease that affects the lungs and digestive system of about 70,000 children and adults worldwide. Cystic fibrosis 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.

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 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.

On a per protocol assessment, acebilustat-treated patients exhibited an 19% reduction in PEx and a 22% reduced risk in progressing to first PEx versus placebo. Additionally, over 40% of patients treated with acebilustat completed the study without experiencing a PEx, an increase of 32% as compared with patients treated with placebo. The benefits of acebilustat on pulmonary exacerbations were apparent as early as four months after start of treatment and persisted throughout the 48 weeks of the study. No difference in lung function, as measured by the primary endpoint of FEV1 percent predicted (FEV1pp), was observed in acebilustat-treated patients compared to placebo-treated patients over 48 weeks of treatment.

Acebilustat is a novel anti-inflammatory molecule evidencing the potential to reduce frequency of pulmonary exacerbations and prolong time to first exacerbation in CF patients.