Key result
Ensifentrine increases peak FEV1 by 200 mL versus placebo at four weeks in COPD.
Why the study?
Many COPD patients continue to experience daily symptoms and exacerbations despite maximal therapy, prompting investigation of the dual PDE 3 and 4 inhibitor ensifentrine.
Does ensifentrine improve peak FEV1 in patients with COPD?
RCT (n=405)
Double-blind
Randomised equally to five treatment groups
Yes
Does ensifentrine improve peak FEV1 in patients with COPD?
Effect estimate: Mean difference 200 mL (for 3 mg dose) (95% CI 131-270)
p-value: p=≤0.0001
In a Phase IIb study, the first-in-class dual PDE3/4 inhibitor ensifentrine significantly improved bronchodilation and symptoms in patients with COPD over 4 weeks.
Ensifentrine improves peak FEV1 in COPD; supports Phase 3 evaluation of dual PDE3/4 inhibition as add-on bronchodilator therapy.
Background Many patients with chronic obstructive pulmonary disease (COPD) still experience daily symptoms, exacerbations, and accelerated lung function decline, even when receiving maximal combined treatment with inhaled long-acting bronchodilators and corticosteroids. Novel treatment options are needed for these patients. Phosphodiesterases (PDEs) are enzymes that impact a range of cellular functions by modulating levels of cyclic nucleotides, and there is evidence to suggest that combined inhibition of PDE3 and PDE4 can have additive (or perhaps synergistic) effects. This study investigated the efficacy and safety of ensifentrine, a first-in-class dual inhibitor of PDE 3 and 4, in patients with COPD. Methods This randomised, double-blind, placebo-controlled, parallel-group, dose-ranging study recruited patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) 40–80% predicted and FEV 1 /forced vital capacity ratio ≤ 0.7. Patients were randomised equally to inhale nebulised ensifentrine 0.75, 1.5, 3 or 6 mg or placebo, all twice daily. Primary outcome: placebo-adjusted difference in peak FEV 1 (assessed over 3 h) at Week 4. Results The study took place between July 2017 and February 2018. Of 405 patients randomly assigned to medication, 375 (92.6%) completed the study. For peak FEV 1 at Week 4, all four ensifentrine doses were superior to placebo ( p ≤ 0.0001) with least squares mean differences of 146 (95% CI 75–216), 153 (83–222), 200 (131–270) and 139 (69–210) mL for ensifentrine 0.75, 1.5, 3 and 6 mg, respectively. Respiratory symptoms (assessed using the Evaluating Respiratory Symptoms questionnaire) were also significantly improved with all ensifentrine doses at Week 4. Adverse events were reported by 33.3, 44.4, 35.4 and 36.3% patients with ensifentrine 0.75, 1.5, 3 and 6 mg, respectively, and 39.2% with placebo. Conclusions In this four-week Phase IIb study, all four ensifentrine doses significantly improved bronchodilation and symptoms, with a dose-ranging effect from 0.75 to 3 mg twice daily, and all doses well tolerated. The study supports the continuing development of ensifentrine in COPD. Trial registration EudraCT 2016–005205-40 , registered 30 May 2017.
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Singh et al. (2020) conducted an RCT in Chronic obstructive pulmonary disease (COPD) (n=405). Ensifentrine vs. Placebo was evaluated on Placebo-adjusted difference in peak FEV1 (assessed over 0-3 h) at Week 4 (Mean difference 200 mL (for 3 mg dose), 95% CI 131-270, p=≤0.0001). Ensifentrine significantly improved bronchodilation compared to placebo in patients with COPD, with the 3 mg twice daily dose increasing peak FEV1 by 200 mL at week 4.
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