Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies

Background: The efficacy and safety of ensifentrine, a novel PDE3/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens. Objective: This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS). Methods: Eligible patients had moderate to severe COPD, were aged 40–80 years, and were symptomatic at randomization. Patients were randomized 5:3, receiving twice-daily ensifentrine 3 mg or placebo via standard jet nebulizer over 24 weeks. Results: The pooled post-hoc analysis included 485 LAMA patients and 272 LABA + ICS patients. Ensifentrine showed lung function improvement over placebo at week 12, including average FEV₁ AUC_0–12 h in the LAMA (placebo-corrected least squares mean change from baseline [LSMC], 92 mL; 95% CI, 54, 131; p < 0.001) and LABA + ICS subgroups (LSMC, 74 mL; 95% CI, 27, 121; p = 0.002). Ensifentrine reduced the rate and risk of exacerbations in both LAMA (48% and 50%, respectively) and LABA + ICS (51% and 56%, respectively) subgroups. Ensifentrine-treated patients reported improvement in symptoms and quality of life over 24 weeks. The safety profile of ensifentrine in each subgroup was similar to the profile in the pooled modified intention-to-treat population. Conclusions: Nebulized ensifentrine offers a novel non-steroidal anti-inflammatory and bronchodilator treatment added to existing LAMA or LABA + ICS treatment options in patients with moderate to severe, symptomatic COPD.