Ensifentrine plus tiotropium improves lung function, quality of life in patients with COPD
Adding ensifentrine to tiotropium demonstrated clinically important improvements in lung function and quality of life at 4 weeks in patients with moderate to severe COPD, according to a new study.
Gary T. Ferguson, MD, pulmonologist at the Pulmonary Research Institute of Southeast Michigan, and colleagues reported data from a phase 2, double-blind, placebo-controlled, parallel-group, dose-ranging study of twice-daily nebulized ensifentrine (Verona Pharma) added to once-daily tiotropium (Spiriva Respimat, Boehringer Ingelheim) in an e-poster presented at the American Thoracic Society Virtual meeting.
Researchers previously completed a placebo-controlled, dose-ranging phase 2 study that showed ensifentrine improved lung function and reduced symptoms in patients with moderate to severe COPD.
In this current study, researchers enrolled 416 patients (mean age, 64.3 years; 42.5% men) with COPD who were current and former smokers ( 10 pack-year history). Enrolled patients remained symptomatic with FEV1 30% to 70% predicted following treatment with tiotropium. Patients were randomly assigned to once-daily tiotropium plus nebulized ensifentrine at one of four doses (0.375 mg, 0.75 mg, 1.5 mg or 3 mg) or placebo twice daily. Spirometry was performed before dosing and over 3 or 12 hours.
Primary endpoint was change from baseline in peak FEV1 at 4 weeks. Other endpoints included average FEV1 over 3 and 12 hours, COPD-related quality of life and safety.
All ensifentrine doses demonstrated significant bronchodilation in addition to tiotropium with a dose-dependent increase from baseline FEV1 at 4 weeks (78 mL to 124 mL; P < .05 for all).
Researchers observed dose-dependent increases in average FEV1 with ensifentrine 3 mg, with an increase to 87 mL (P = .0111). Patient responses to the St. George’s Respiratory Questionnaire showed clinically meaningful and statistically significant improvement in quality of life exceeding 4 U at 4 weeks with ensifentrine 1.5 mg and 3 mg (P < .05 for both).
Adverse events were similar across all groups.
“These data support progression of ensifentrine to phase 3 as a maintenance treatment for COPD,” the researchers wrote in the study abstract.
Ensifentrine is a first-in-class, inhaled dual phosphodiesterase 3/4 inhibitor that combines bronchodilator and anti-inflammatory actions in a single compound.
According to a press release from Verona Pharma, preparations for the phase 3 clinical programs are underway following response from the FDA and are expected to begin in late 2020. The two studies, ENHANCE-1 and ENHANCE-2, will assess the safety and efficacy of twice-daily nebulized ensifentrine as monotherapy and as an add-on to standard treatment with a single bronchodilator, a long-acting muscarinic antagonist or a long-acting beta agonist.