Phase 2b Study Supports Icenticaftor for Patients with COPD, Chronic Bronchitis

Frits Franssen, MD, PhD

According to data presented at the European Respiratory Society (ERS) International Congress 2022, over a period of 24 weeks the bioavailable small molecule cystic fibrosis transmembrane conductance regulator (CFTR) potentiator icenticaftor (QBW251) improved symptoms in patients with COPD and chronic bronchitis who were on standardized inhaled triple therapy.

Airway homeostasis becomes disrupted when the CFTR is dysfunctional, leading to the worsening of COPD symptoms. Frits Franssen, MD, PhD, Maastricht University, led investigators in conducting a phase 2b study to evaluate the optimal dosage of icenticaftor for this population of patients.

“Chronic bronchitis is a key phenotype in patients with COPD,” Franssen explained in his presentation at ERS Congress 2022. “However, currently available COPD treatments do not address every day symptoms such as cough and sputum in COPD. 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 Phase 2b Study

This multi-centre, parallel-group, double-blind study compared the novel, oral CFTR potentiator icenticaftor with placebo in a model-based approach. The observed population consisted of patients with COPD and chronic bronchitis who have a history of exacerbations.

The treatment, or placebo, was administered twice a day to 974 patients in conjunction with standardized inhaled triple therapy (LABA/LAMA/ICS) for a period of 24 weeks. Randomization was used to designate 6 treatment arms that received icenticaftor 450mg, 300mg, 150mg, 75mg, 25mg, or placebo.

The Endpoints

The primary endpoint was the trough FEV1 change, or the mean volume of air that a patient can reach on a spirometry after a set amount of time following drug administration, measured from baseline after 12 weeks.

As for the secondary endpoints, investigators assessed EXACT-Respiratory Symptoms (E-RS) total score and E-RS cough and sputum (C&S) score after 24 weeks. The use of rescue medication after 6 months was included as an exploratory endpoint.

The Observed Dose Responses

Investigators reported that after 12 weeks, no response in FEV1 was observed among any dose, leaving the primary endpoint unmet. However, after 24 weeks, a response was observed among those who received icenticaftor 300mg BID.

Icenticaftor 300mg demonstrated consistent improvements for FEV1 and EXACT-Respiratory Symptoms and cough and sputum total scores, meeting the secondary endpoints. The exploratory endpoint was also fulfilled by the 300mg dose when rescue medication use after 6 months was examined.

All treatments were well-tolerated.

“Icenticaftor demonstrated a favorable safety profile and from this study it makes sense that the 300mg dose has a benefit-risk profile to further study the clinical benefits of this dose in patients with COPD and a phenotype of chronic bronchitis,” Franssen said in conclusion.