Lung Function and Safety Outcomes in Patients With Moderate-to-Severe COPD Treated With Ensifentrine: A Pooled...

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.

Does ensifentrine improve lung function among patients with COPD?

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.

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.

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.