Efficacy and Safety of Ensifentrine in Chinese Patients with Chronic Obstructive Pulmonary Disease: The ENHANCE-CHINA Randomized Clinical Trial.

Zhou, Yumin; Chen, Charlie; Wang, Zihui; Wu, Fan; Tian, Dongbo; Xiao, Zuke; Cao, Jie; Xu, Feng et al. · Chest · 2026

rct · Level II

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Abstract

Ensifentrine, a novel phosphodiesterase 3/4 inhibitor, significantly improved lung function and reduced chronic obstructive pulmonary disease (COPD) exacerbations in previous trials in Western populations. However, efficacy and safety data on its use in participants with COPD in China remain limited. Is nebulized ensifentrine effective and safe compared with placebo for the treatment of COPD in Chinese participants? A phase III multicenter, randomized, double-blind, placebo-controlled trial was conducted between March 2023 and March 2025. The study enrolled participants with moderate-to-severe symptomatic COPD randomized to the ensifentrine group or the placebo group (5:3) over 24 weeks and stratified by maintenance therapy and smoking status. The primary endpoint was lung function improvement measured by forced expiratory volume in 1 second (FEV<sub>1</sub>) area under the curve at 0-12 hours (AUC<sub>0-12h</sub>). Other endpoints included quality of life, symptoms, and exacerbations. Overall, 525 participants were included in the analysis, with 45.9% receiving concomitant maintenance therapy. Ensifentrine significantly improved average FEV<sub>1</sub> AUC<sub>0-12h</sub> versus placebo (110 mL, 95% confidence interval: 69-151 mL, P<0.0001). Lung function improvement was consistent across clinically relevant subgroups, including participants with and without maintenance therapy, as well as participants with moderate and severe COPD. Ensifentrine significantly improved Transition Dyspnea Index and showed improvements in Evaluating Respiratory Symptoms and St. George's Respiratory Questionnaire scores versus placebo. Ensifentrine treatment tended to reduce the rate of moderate-to-severe exacerbations and increased the time to first exacerbation. Adverse event rates were similar between the ensifentrine and placebo groups. Ensifentrine significantly improved lung function and showed efficacy benefits in symptoms, quality of life improvement, and exacerbation reduction in Chinese individuals with COPD.