Ensifentrine, a novel dual phosphodiesterase (PDE) 3 and 4 inhibitor, provides effective bronchodilation when administered by dry powder inhaler in COPD

Ensifentrine (RPL554) is an investigational, first-in-class, inhaled dual inhibitor of the enzymes PDE 3 and 4 that combines bronchodilator and anti-inflammatory actions in a single compound. In previous trials, nebulised ensifentrine delivered clinically meaningful and significant improvements vs placebo in lung function and symptoms in COPD. This parallel group, single dose study reports the effect of ensifentrine administered by dry powder inhaler in patients with COPD. We examined the bronchodilator effects, safety and tolerability of single-dose ensifentrine (150, 500, 1500, 3000 and 6000 µg) vs placebo in 37 patients (mean age 59.5 years [45–74], 37.8% male). Patients demonstrated post-bronchodilator (4 puffs of salbutamol) FEV₁/FVC ratio ≤0.70, FEV₁≥40% and ≤80% of predicted normal and ≥150 mL increase from pre-bronchodilator FEV₁. After a single dose, ensifentrine provided effective and dose-dependent bronchodilation, in terms of the mean change from baseline in average and peak FEV₁ over 4 hours (Table). No significant adverse events were reported, and there were no statistical differences from placebo for heart or pulse rate for any ensifentrine dose. This study demonstrates that ensifentrine administered by dry powder inhaler can be an effective and convenient treatment for patients with COPD. Funded by Verona Pharma plc. Table. Change from baseline in average and peak FEV₁ over 4 hours