Ensifentrine improved symptoms and reduced moderate/severe exacerbation rate and risk in patients with COPD and significant cough and sputum

Intro: Ensifentrine is a first-in-class, inhaled dual inhibitor of PDE3/4 with bronchodilation and anti-inflammatory effects. These data report the effect of ensifentrine in patients with COPD and significant cough and sputum symptoms. <bold>Methods:</bold> The ENHANCE trials were 2 Phase 3, global, randomized, double-blind, placebo-controlled trials that studied the effect of nebulized ensifentrine twice daily in patients age 40-80 years with symptomatic, moderate to severe COPD (FEV₁ 30-70% predicted; mMRC ≥2). A post-hoc pooled analysis of patients with significant cough/sputum at baseline (E-RS cough and sputum subdomain ≥mean; 3.55) was conducted to evaluate symptom improvement and moderate/severe exacerbations. <bold>Results:</bold> Baseline demographics were similar between ensifentrine (n=473) and placebo (n=255) groups, including age, COPD severity, background medications, smoking status, chronic bronchitis, and E-RS baseline total scores. Ensifentrine resulted in significantly improved E-RS cough and sputum subdomain scores (exceeding the minimal clinically important difference of -0.7) vs placebo, occurring by Week 12 (least-squares mean [LSM] difference vs placebo -0.25; p=0.02) and sustained through Week 24 (LSM difference -0.31; p=0.01). Over 24 weeks, ensifentrine reduced the rate of (42%, p<0.01) and prolonged the time to first (41%, p<0.01) moderate/severe exacerbation vs placebo. The safety profile of ensifentrine was similar to placebo and overall adverse event rates were low. Conclusion: In a subset of patients with COPD and significant cough and sputum symptoms at baseline, ensifentrine improved those symptoms while also reducing exacerbations.