Ensifentrine treatment improves COPD symptoms and quality of life in a pooled analysis of the ENHANCE trials

<bold>Intro:</bold> Despite availability of many COPD treatment options, patients with COPD continue to experience significant symptom burden. Ensifentrine is a first-in-class, selective, dual inhibitor of phosphodiesterase (PDE)3 and PDE4 with bronchodilation and non-steroidal anti-inflammatory effects. <bold>Methods:</bold> The ENHANCE trials were two Phase 3, global, multicenter, randomized, double-blind, placebo-controlled, 24-week trials conducted in symptomatic patients age 40-80 years with moderate-to-severe COPD (post-bronchodilator FEV1 30–70% predicted, mMRC ≥2, <ext-link>NCT04542057</ext-link> & <ext-link>NCT04535986</ext-link>). Post-hoc pooled analyses (N=1549) were conducted to evaluate effects of ensifentrine on COPD symptoms, as measured by the Evaluating-Respiratory Symptoms [E-RS] and quality of life, as measured by the St. George’s Respiratory Questionnaire (SGRQ). <bold>Results:</bold> Treatment with nebulized ensifentrine resulted in significant improvements vs placebo in COPD symptoms as measured by E-RS total score as early as week 6 which were sustained through weeks 12 and 24 (p<0.05). Patients who received ensifentrine also experienced larger improvements vs placebo in SGRQ total score at weeks 6, 12, and 24 (p<0.05 for weeks 6 and 12). Greater improvements with ensifentrine vs placebo were also seen at week 24 for all subdomains of both E-RS and SGRQ. At week 24, 46% of patients who received ensifentrine were considered responders to the E-RS (change from baseline [CFB] ≥-2) and 52% were responders to SGRQ (CFB ≥-4). <bold>Conclusion:</bold> Treatment with nebulized ensifentrine produced early, sustained, and clinically meaningful improvements in symptoms and quality of life measures in patients with moderate-to-severe COPD.