Ensifentrine Monotherapy Improves Dyspnea, Health-Related Quality of Life in COPD

New research is shedding light on the impact of ensifentrine monotherapy on patient-reported outcomes in individuals with chronic obstructive pulmonary disease (COPD).1

Findings from the analysis of data from the phase 3 ENHANCE trials of nebulized ensifentrine were presented at the American Thoracic Society (ATS) International Conference 2025 by Michael Bradley Drummond, MD, co-medical director of UNC Pulmonary Specialty Clinics and director of the Obstructive Lung Diseases Clinical and Translational Research Center at UNC School of Medicine, and highlight improved dyspnea, COPD symptoms and health-related quality of life, and reduced rescue medication use versus placebo in patients not taking long-acting COPD medications.1

“Patients with COPD experience significant disease burden, with up to 50% of US patients reporting bothersome symptoms that impact their daily lives,” Drummond and colleagues wrote.1 “While many of these patients are treated with long-acting bronchodilators, there remains a substantial proportion of patients that are not yet treated with maintenance medications.”

Ensifentrine, an inhaled nonsteroidal nebulizer therapy, was approved by the US Food and Drug Administration for the treatment of COPD in 2024. The approval of the dual inhibitor of the phosphodiesterase 3 and 4 pathways was supported by data from the phase 3 ENHANCE clinical trial program—a pair of randomized, double-blind, placebo-controlled trials including approximately 800 patients with moderate to severe, symptomatic COPD across North America and Europe.2

The present analysis assessed pooled patient-reported outcome results in patients who were not on a background maintenance therapy during the ENHANCE trials. Both were conducted in symptomatic patients 40–80 years of age with moderate-to-severe COPD, defined as FEV1 30–70% predicted; FEV1/FVC <0.7; mMRC ≥2.1

Patients were randomized in a 5:3 ratio to receive nebulized ensifentrine 3 mg or placebo twice daily via standard jet nebulizer for 24 weeks. Randomization was stratified by whether or not patients were on long-acting background medication, and all patients were provided a short acting bronchodilator to treat symptoms as needed.1

Secondary endpoints included Transition Dyspnea Index (TDI), Evaluating-Respiratory Symptoms (E-RS) Total Score and St. George’s Respiratory Questionnaire (SGRQ) Total Score at weeks 6, 12 and 24.1

In total, the pooled ENHANCE trials included 975 ensifentrine-treated and 574 placebo-treated patients. The present analysis included 369 (38%) ensifentrine-treated and 222 (39%) placebo-treated patients without concomitant background therapy.1

Investigators noted TDI was significantly improved at all weeks with ensifentrine monotherapy versus placebo (week 24 ensifentrine least-squares mean, 2.0; 95% CI, 1.6 to 2.3 vs placebo least-squares mean, 1.1; 95% CI, 0.7 to 1.5; P <.05). Additionally, E-RS Total Score was reduced with ensifentrine monotherapy versus placebo at weeks 6, 12, and 24. Ensifentrine also significantly improved SGRQ Total Score compared with placebo at weeks 6 and 12 (P <.05), with numerical improvements vs placebo at Week 24.1

Compared with placebo, those treated with ensifentrine monotherapy had less rescue medication use compared with placebo at weeks 6, 12, and 24 (P <.05 for all; week 24 LS mean change from baseline, -0.86 vs -0.36 average daily puffs).1

“Ensifentrine improved dyspnea, COPD symptoms and health-related quality of life, and reduced rescue medication use vs placebo in patients not taking long-acting COPD medications,” investigators concluded.1 “Nebulized ensifentrine offers a novel, non-steroidal mechanism that can provide meaningful improvements as a monotherapy in patients with symptomatic, moderate-to-severe COPD.”

References

1. Drummond MB, Rheualt T, Biney IN, et al. Ensifentrine Monotherapy Reduced Dyspnea and Improved Quality of Life in Patients With Symptomatic, Moderate-to-Severe COPD. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.

2. Kunzmann K. FDA Approves Ensifentrine (Ohtuvayre) for COPD. HCPLive. June 26, 2024. Accessed May 19, 2025. https://www.hcplive.com/view/fda-approves-ensifentrine-for-copd