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, firstin-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-tosevere 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 FEV 1 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 FEV 1 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 < .0001for all time points).Ensifentrine also demonstrated significant improvements across all other lung function parameters, including average FEV 1 area under the curve from administration time to 4 hours (LS mean difference, 137 mL at week 12; P < .0001for all time points), FEV 1 area under the curve from 6 hours to 12 hours (LS mean difference, 59 mL at week 12; P < .0001),morning trough FEV 1 (LS mean difference, 42 mL at week 12; P < .001),and evening trough FEV 1 (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.