Lung Function and Safety Outcomes in Patients With Moderate-to-Severe COPD Treated With Ensifentrine

Background Despite the use of maintenance therapies, many patients with COPD continue to experience persistent symptoms and impaired lung function. Ensifentrine is a novel, first-in-class selective dual inhibitor of phosphodiesterase (PDE) 3 and PDE4 with demonstrated nonsteroidal antiinflammatory activity and bronchodilatory effects. Research Question Does ensifentrine improve lung function among patients with COPD? Study Design and Methods This prespecified, pooled analysis of the phase 3, multicenter, randomized, double-anonymized, placebo-controlled Ensifentrine as a Novel Inhaled Nebulized COPD Therapy (ENHANCE-1 [NCT04535986] and ENHANCE-2 [NCT04542057]) trials evaluated the effect of ensifentrine on lung function and safety outcomes. The trials included patients 40 to 80 years of age with symptomatic moderate-to-severe COPD who received 3 mg twice-daily ensifentrine or placebo for 24 weeks. Results The pooled analysis included 975 patients treated with ensifentrine and 574 patients who received placebo. Ensifentrine significantly improved average FEV₁ area under the curve over 12 hours at week 12 from baseline vs placebo (least squares [LS] mean difference, 90 mL). Rapid improvements in peak FEV₁ were observed with ensifentrine treatment as early as day 1 (LS mean difference, 154 mL), which were sustained through week 24 compared with placebo (LS mean difference, 135 mL) ( P < .0001 for all time points). Ensifentrine also demonstrated significant improvements across all other lung function parameters, including average FEV₁ area under the curve from administration time to 4 hours (LS mean difference, 137 mL at week 12; P < .0001 for all time points), FEV₁ area under the curve from 6 hours to 12 hours (LS mean difference, 59 mL at week 12; P < .0001), morning trough FEV₁ (LS mean difference, 42 mL at week 12; P < .001), and evening trough FEV₁ (LS mean difference, 56 mL at week 12; P < .0001). Ensifentrine was well tolerated, with adverse event rates similar to placebo. Interpretation Ensifentrine demonstrated early, sustained, and clinically significant improvements in lung function in a broad population and across all subgroups of patients with symptomatic moderate-to-severe COPD.