Efficacy and safety of ensifentrine in European patients with moderate to severe COPD: pooled results from the ENHANCE trials

<bold>Introduction:</bold> Efficacy and safety of dual phosphodiesterase inhibitor ensifentrine was demonstrated in the ENHANCE trials in COPD patients from 17 countries. Since responses may differ between populations, this subgroup analysis focused on European patients. <bold>Methods:</bold> A post-hoc pooled analysis was conducted to evaluate lung function, patient-reported outcomes (Week 24 E-RS, TDI, and SGRQ), exacerbations (Week 24 rate and risk), and safety in European patients from the ENHANCE trials. These included symptomatic patients with moderate to severe COPD in a global, multicenter, randomized, double-blind design that studied nebulized ensifentrine 3 mg twice daily vs placebo. <bold>Results:</bold> 913 European patients were included. Relevant clinical characteristics were comparable between groups at baseline. Ensifentrine significantly improved lung function vs placebo at Week 12 (FEV₁ AUC_0-12h, p<0.0001; peak FEV₁, p<0.0001; morning trough FEV₁, p=0.002). Significant and sustained improvements in E-RS and TDI total scores were observed at Weeks 6, 12, and 24 for ensifentrine vs placebo (p<0.01 for all). Improvements beyond the minimal clinically important difference (≥-4) in SGRQ total score were also demonstrated with ensifentrine vs placebo at Weeks 6, 12, and 24. Ensifentrine reduced the rate (45%, p=0.0058) and risk (49%, p=0.002) of moderate/severe exacerbations over 24 weeks vs placebo. The safety profile of ensifentrine was similar to placebo, and overall adverse event rates were low. <bold>Conclusion:</bold> Ensifentrine improved lung function, patient-reported outcomes, and exacerbation rate and risk in symptomatic European patients with moderate to severe COPD.