Ensifentrine for COPD maintenance treatment

Dr Dave Singh (University of Manchester, UK) reported on the 4-week, placebo-controlled, dose-ranging study, with patients sub-grouped by baseline reversibility of lung function measured pre- and post-albuterol administration [1]. The results show continued symptom benefits of treatment that improve over time, supporting anti-inflammatory effects in addition to bronchodilation. This phase 2b clinical trial supports ensifentrine for the maintenance treatment of chronic obstructive pulmonary disease (COPD) and is planned to enter phase 3 trials in 2020.

Ensifentrine is an inhaled dual inhibitor of the enzymes phosphodiesterase 3 and 4, and the researchers hypothesised that its activity as a bronchodilator and an anti-inflammatory agent would be clinically relevant to COPD patients. The study recruited a total of 403 diagnosed COPD patients (mean age 63.2 years), who were grouped by reversibility of their disease: 133 (33%) patients were in the reversible subgroup, and 270 (67%) patients in the non-reversible subgroup. Reversible patients had a pre- to post-bambuterol change in FEV1 at screening of ≥200 mL and ≥12%; non-reversible patients had a change of <200 mL or <12%. Baseline characteristics were similar between the 2 subgroups. Eligible patients were randomised to ensifentrine 0.75 mg, 1.5 mg, 3 mg, or 6 mg or placebo twice daily for 4 weeks. Forced expiratory volume in 1 second (FEV1) was assessed at baseline, on day 1, and every week thereafter.

All ensifentrine doses significantly increased peak FEV1 0-3h vs placebo in both subgroups, with consistent efficacy from week 1 onwards. Notably, the improvement in peak FEV1 was greater in the reversible than the non-reversible subgroup. Ensifentrine improved COPD symptoms in both the reversible and non-reversible subgroups, with an effect at or near the minimal clinically important difference by week 4. Overall, ensifentrine was well tolerated, with all doses having an adverse event profile similar to placebo (33.3 to 44.4% with ensifentrine compared with 39.2% with placebo).

The authors concluded that all ensifentrine doses provided significant improvements in lung function, with a greater effect in the reversible subgroup than the non-reversible subgroup, and with the effect continuing to improve over 4 weeks. Dr Sing speculated that the observed progressive improvement in symptoms may be due to combined anti-inflammatory effect and bronchodilation leading to greater lung deflation.

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   1. Singh D et al, RPL554 (Dual PDE3/4 Enzyme Inhibitor): Baseline Airway Reversibility Impacts Immediate Bronchodilation, in Contrast to Progressive Symptom Improvement. A3846 ATS 2019, 17-22 May, Dallas, USA.

Posted on 23 July 201924 March 2021