Effect of ensifentrine on dyspnea in patients with moderate-to-severe chronic obstructive pulmonary disease: pooled analysis of the ENHANCE trials

Abstract

Background: Dyspnea is a critical component of chronic obstructive pulmonary disease (COPD). We report the effect of ensifentrine, a novel PDE3/PDE4 inhibitor, on dyspnea using pooled data from the Phase 3 ENHANCE-1/2 trials.

Methods: The pooled population (ensifentrine, n = 975; placebo, n = 574) included patients aged 40-80 years with post-bronchodilator FEV₁/FVC <0.7, FEV₁ 30-70% predicted, mMRC Dyspnea Scale score ≥2, and a smoking history ≥10 pack-years. Patients taking dual LAMA/LABA or LAMA/LABA/ICS triple therapy were excluded. Dyspnea measures included the Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms (E-RS), and rescue medication use.

Results: After 24 weeks, ensifentrine significantly improved TDI scores (least-squares mean difference, 0.97; 95% CI, 0.64, 1.30; p < 0.001) and across all TDI subdomains. Ensifentrine-treated patients were more likely to be TDI responders at week 24 (p < 0.001), which was consistent across clinically relevant subgroups. Ensifentrine-treated patients had improved E-RS breathlessness subdomain scores (p = 0.053) and reduced rescue medication use (p = 0.002).

Conclusion: Ensifentrine produced clinically meaningful improvements in multiple dyspnea measures in patients with symptomatic, moderate-to-severe COPD. A limitation of this study was the exclusion of patients taking dual LAMA/LABA and LAMA/LABA/ICS triple therapy.

Clinical trial registration: www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.

Keywords: Dyspnea; PDE3 inhibitor; PDE4 inhibitor; chronic obstructive pulmonary disease; ensifentrine.