Ensifentrine improved lung function and reduced moderate/severe exacerbation rate and risk in patients with COPD regardless of chronic bronchitis history

Ensifentrine is a first-in-class, inhaled dual inhibitor of PDE3 and PDE4 with demonstrated bronchodilation and anti-inflammatory effects. <bold>Methods:</bold> The ENHANCE trials were two Phase 3, global, multicenter, randomized, double-blind, placebo-controlled trials that studied the effect of ensifentrine in patients with symptomatic, moderate to severe COPD (FEV₁ 30–70% predicted; mMRC ≥2). A post-hoc pooled analysis of lung function and exacerbations was conducted in patients (N=1549) with or without a history of chronic bronchitis (CB). CB was assessed by the investigator or medical professional and defined as “regular production of sputum for ≥3 months in 2 consecutive years (in the absence of other conditions that may explain it [GOLD, 2020]).” Results: The pooled population consisted of 1112 patients with a history of CB (ensifentrine, n=707; placebo, n=405) and 437 patients without (ensifentrine, n=268; placebo, n=169). A significantly greater improvement in Week 12 FEV₁ AUC_0-12h and peak FEV₁ (p<0.001 for all) occurred in patients who received ensifentrine vs placebo, in patients with and without CB. Over 24 weeks, the rate of moderate/severe exacerbations was reduced with ensifentrine vs placebo by 37% (p<0.05) in the CB subgroup and 44% (p<0.05) in those without CB. The risk of a moderate/severe exacerbation was reduced vs placebo by 35% (p<0.05) in the CB group and 49% (p<0.05) in those without CB. <bold>Conclusion:</bold> Significant improvement in lung function and reduction in rate and risk of moderate/severe exacerbations was demonstrated when ensifentrine was added to patients with COPD with or without a history of CB.