Icenticaftor shows promise for patients with COPD, chronic bronchitis
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Icenticaftor did not yield a dose response for trough FEV1 at 12 weeks, but treatment was associated with improved symptoms at 24 weeks in patients with COPD and chronic bronchitis on inhaled triple therapy, researchers reported.
Icenticaftor (Novartis) is an oral cystic fibrosis transmembrane conductance regulator potentiator that restores lung function with benefits in airway cell function, lung health, mucus plugging and patient benefits such as symptom and exacerbation reduction.
“Chronic bronchitis is a key phenotype in patients with COPD. However, currently available COPD treatments do not address everyday symptoms such as cough and sputum in COPD,” Frits M.E. Franssen, PhD, professor of personalized management of COPD in the department of respiratory medicine at Maastricht University Medical Centre, the Netherlands, said during the presentation at the European Respiratory Society International Congress. “We know, however, that higher levels of cough and sputum are associated with poor outcomes in COPD in terms of quality of life, accelerated lung function decline, exacerbations and mortality.”
The multicenter, double-blind, placebo-controlled study included 974 patients with COPD and chronic bronchitis (mean age, 66.6 years; 61.7% men). All patients had at least 10 pack-years of smoking history, were receiving inhaled triple therapy with long-acting beta 2 agonists/long-acting muscarinic antagonists/inhaled corticosteroids for at least 3 months, had a COPD Assessment Test (CAT) score higher than 10 and had Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 or 3 with at least one exacerbation in the past year. Patients were randomly assigned daily oral icenticaftor 450 mg (n = 99), 300 mg (n = 250), 150 mg (n = 124), 75 mg (n = 126) or 25 mg (n = 124) or placebo for 24 weeks.
The primary outcome was change in trough FEV1 from baseline to week 12. Secondary outcomes included change from baseline to week 24 in trough FEV1, EXACT-Respiratory Symptoms (E-RS) total score, E-RS cough and sputum score. Researchers also evaluated rescue medication use and fibrinogen levels at week 24 as an exploratory endpoint.
According to Franssen, the 450 mg icenticaftor arm was discontinued prematurely due to predefined stopping criterion.
Researchers reported no dose response for trough FEV1 at 12 weeks.
However, a dose response was achieved at 24 weeks for trough FEV1, E-RS total scores, E-RS cough and sputum and rescue medication. At 24 weeks, 300 mg icenticaftor was consistently the most effective dose, Franssen said, with 0.035 L improvement in trough FEV1 compared with placebo. Similar trends were observed for total E-RS score and E-RS cough and sputum scores for icenticaftor 300 mg. Results also showed a reduction in fibrinogen and daily rescue medication over 24 weeks.
Icenticaftor demonstrated a favorable safety and tolerability profile at all doses tested, Franssen said. No major safety concerns were observed in any treatment group. About 60% of patients experienced at least one adverse event; the most common events were related to COPD.
“Improvement in endpoints is on top of maximum inhaled triple therapy, which is currently considered to provide maximum bronchodilation and anti-inflammatory benefit. ... From this study, it makes sense that the 300 mg dose [has] a positive benefit-risk profile [and] to further study the clinical benefits of this dose in patients with COPD and a phenotype of chronic bronchitis,” Franssen said.