People with COPD suffer from daily symptoms and impaired quality of life, and COPD treatments to address these burdens are needed. Ensifentrine, a novel dual inhibitor of phosphodiesterase (PDE)3 and PDE4, improves symptoms, dyspnea, and quality of life in patients with COPD, regardless of whether they experience exacerbations.
The researchers conducted a post hoc analysis of the two global phase 3 ENHANCE trials to evaluate the effect of ensifentrine on symptoms, dyspnea, and quality of life in patients who did not have exacerbations during the trials.
The randomized controlled double-blind ENHANCE trials evaluated nebulized ensifentrine 3 mg twice daily in patients aged 40 to 80 years who had symptomatic, moderate-to-severe COPD (FEV 1 30-70% predicted, mMRC ≥2, smoking history ≥10 pack-years), with stable background maintenance bronchodilator medication permitted.
The ENHANCE trials investigated the change from baseline to week 12 average FEV 1 AUC 0-12. The trials also analyzed the Transition Dyspnea Index (TDI) Score, Evaluating-Respiratory Symptoms (E-RS) Total Score, and St. George’s Respiratory Questionnaire (SGRQ) Total Score at Weeks 6, 12, and 24.
The post-hoc pooled analysis examined dyspnea, symptoms, and quality of life in a subgroup of 1,384 participants who did not experience moderate or severe COPD exacerbations during the 24-week trial period.
Of the 1,384 patients who did not experience exacerbations during the ENHANCE trials, 891 received ensifentrine and 493 received placebo. Demographics and baseline characteristics were similar between the groups.
Sustained Improvements Observed Across Multiple Measures
Participants treated with ensifentrine showed significant, long-term improvements in TDI Score compared to those on placebo at Weeks 6, 12, and 24 (P<0.05). Patients who received ensifentrine were significantly more likely to have a clinically meaningful improvement in TDI Score (minimal clinically important difference [MCID] ≥ 1 unit) at all time points (P<0.05). They were also likely to have significantly greater E-RS Total Scores at Weeks 6, 12, and 24 compared to those on placebo (P<0.05).
A significantly greater proportion of participants taking ensifentrine were responders in E-RS Total Score compared to those on placebo (MCID≥-2) at Weeks 6 and 12 (P<0.05). Also, a numerically greater proportion of participants in the ensifentrine group were responders in the E-RS Total Score at Week 24.
SGRQ total score among the patients on ensifentrine improved vs placebo at all time points, and ensifentrine had a significantly greater proportion of SGRQ responders (MCID ≥-4) versus placebo at Weeks 6 and 12 (P<0.05), as well as a numerically greater proportion of SGRQ responders versus placebo at Week 24.
Reference
Hanania NA, Rheault T, Dixon A, et al. Ensifentrine Improved Symptoms, Dyspnea, and Quality of Life in Patients With COPD Who Did Not Exacerbate During the ENHANCE Trials. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
