After 24 weeks, the use of icenticaftor on top of triple inhalation therapy resulted in a clear dose-response on 5 endpoints in patients with COPD and chronic bronchitis. The 300 mg, twice-daily dose of the drug showed an encouraging benefit-risk profile and should be investigated in further trials.
A phase 2b trial (NCT02449018), conducted by Prof. Frits Franssen (Maastricht University, the Netherlands) and co-investigators, assessed the dose-response relationship of the orally-active, CFTR channel potentiatior icenticaftor on top of a triple therapy of long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled corticosteroids (ICS) in patients with COPD (severity class GOLD 2 & 3) and chronic bronchitis (n=974) . The trial included 5 icenticaftor arms, with doses ranging from 25 mg, twice daily, to 450 mg, twice daily, and a placebo arm. The primary endpoint was the change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 12.
The 450 mg arm of the study discontinued early for meeting a pre-specified, exposure-based stopping criterion. The 300 mg arm displayed the best efficacy results. Although the primary endpoint was not met, the 300 mg arm outperformed placebo with respect to trough FEV1 levels at 24 weeks (least-squares mean 35 mL; 90% CI 0.0008–0.062). Other endpoints showed similar results for the 300 mg arm after 24 weeks of therapy: change in EXACT-Respiratory Symptoms (E-RS) cough and sputum score (-0.40), E-RS total score (-0.85), fibrinogen (-0.332), and number of daily puffs of rescue medication (-0.30).
No major safety concerns were observed for any of the treatment arms. Approximately 61% of the participants experienced at least 1 adverse event (AE), the most common being COPD exacerbations, diarrhoea, nausea, and nasopharyngitis.
Prof. Franssen emphasised that these results were obtained on top of maximum inhaled triple therapy. “The positive benefit-risk profile of the 300 mg, twice daily dose of icenticaftor supports further evaluation of this agent in patients with COPD and chronic bronchitis. Furthermore, we should look for a biomarker that helps us to select patients that are likely to benefit from additional icenticaftor.”
- Franssen FME, et al. Dose response of icenticaftor in patients with COPD and chronic bronchitis on triple inhaled therapy. ALERT 1, RCT710, ERS International Congress 2022, Barcelona, Spain, 4–6 September.
Copyright ©2022 Medicom Medical Publishers
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Table of Contents: ERS 2022
Letter from the Editor
ERS 2022 Highlights Podcast
COVID-19: What Is New?
Does vilobelimab reduce mortality in severe COVID-19?
Awake proning not positive in COVID-19
Favipiravir may help patients over 60 years with COVID-19 to recover
Brensocatib fails in severe COVID-19
Inhaled agent under investigation for COVID-19
Accurate voice-based COVID-19 diagnostic test in development
Novel scoring tool for post-COVID syndrome aids clinicians and researchers
COPD: Therapies and Innovations
Icenticaftor achieves results on top of triple inhalation therapy in COPD
STARR2: A new approach for treating COPD exacerbations
COPD medication not effective in symptomatic smokers with preserved spirometry
Do digital tools improve physical activity in COPD?
Hyperpolarised gas MRI ready for clinical use
All About Asthma
Tezepelumab in asthma: mucus plugging down, lung function up
Digital asthma intervention improves health and reduces costs
Digitally enhanced therapy lowers treatment burden and costs in severe asthma
Mepolizumab beneficial for patients with severe eosinophilic asthma
Progress in Paediatrics
Antibiotics cause increased risk of wheezing in severe RSV bronchiolitis
Inhaled corticosteroids useful in preterms with decreased lung function
Fish oil or vitamin D during pregnancy can prevent croup
Encouraging results of nintedanib in children with fibrosing ILD
Focus on Interventional Pulmonology
Head-to-head: lung volume reduction surgery vs endobronchial valves
Durable effect of endobronchial valves in severe emphysema
Cone beam CT-guided ENB improves detection of pulmonary nodules
Confirmatory mediastinoscopy not needed in resectable NSCLC
Sleep and Breathing Disorders
In the spotlight: Cancer trends in obstructive sleep apnoea
Impact of CPAP on cardiac endpoints in OSA
Sustained hypoxaemia predicts unprovoked VTE in OSA
CPAP therapy in the prevention of cardiovascular risk in patients with OSA
Other Remarkable Research
Excellent results for high-flow nasal cannula oxygen therapy in acute respiratory failure
Antifibrotic therapy may slow down FVC decline in RAILD
Intravenous N-acetylcysteine performs well in hospitalised patients
Men and women respond differently to diesel exhaust
New trends in cystic lung diseases
PAGANINI phase 2b data promising for eliapixant