Symptom Improvement Following Treatment with the Inhaled Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine in Patients with Moderate to Severe COPD – A Detailed Analysis

Abstract

Introduction

Ensifentrine is an inhaled first-in-class dual inhibitor of phosphodiesterase (PDE) 3 and 4. In a four-week randomized, double-blind, placebo-controlled, parallel-group study in patients with chronic obstructive pulmonary disease (COPD), nebulized ensifentrine 0.75 to 6mg twice daily significantly improved bronchodilation and symptoms, with all doses being well tolerated. Here, we report data for a number of prespecified exploratory and post hoc endpoints from this study that help to further profile the effect of ensifentrine on symptoms.

Methods

Eligible patients were males or females aged 40–75 years with COPD, post-bronchodilator forced expiratory volume in 1 second 40–80% predicted. Other than being clinically stable for at least four weeks prior to entry, there were no symptomatic inclusion or exclusion criteria. The outcome measures reported in this manuscript are the Evaluating Respiratory Symptoms [E-RS™:COPD] questionnaire total score and subscales (breathlessness, cough/sputum and chest symptoms) at Weeks 1–4, Transition Dyspnea Index (TDI) focal score at Weeks 2 and 4, and St George’s Respiratory Questionnaire – COPD Specific (SGRQ-C) total score and domain data (symptoms, activity and impacts) at Week 4.

Results

There was a gradual improvement versus placebo with all ensifentrine doses for all three E-RS™:COPD subscales from Week 1 to Week 4, with the greatest ensifentrine effect on the breathlessness subscale, and all four doses superior to placebo from Week 2 onwards (p<0.05). For TDI focal score, all ensifentrine doses were superior to placebo at Weeks 2 and 4 (p<0.05). In the individual SGRQ-C domains at Week 4, ensifentrine had the greatest effect on the symptoms domain, with ensifentrine 6mg superior to placebo (p<0.05).

Conclusion

In these analyses, ensifentrine demonstrated a notable early and meaningful effect on dyspnea, with this effect observed across two different assessment tools.

Keywords:

• phosphodiesterase inhibitors
• chronic obstructive pulmonary disease
• signs and symptoms
• respiratory
• drug therapy

Acknowledgments

Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). The authors would like to thank the investigators and patients at the investigative sites for their support of this study. Writing support was provided by David Young of Young Medical Communications and Consulting Ltd. This support was funded by Verona Pharma plc.

Data Sharing Statement

Deidentified data from this study are available on request, following submission of a valid research protocol to the corresponding author.

Ethics Approval and Informed Consent

The study was approved by independent ethics committees at each institution (see supplement). All patients provided written informed consent prior to any study-related procedure.

Disclosure

HW reports personal fees from AstraZeneca, Bayer, BerlinChemie, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche, all outside the submitted work. KR and TR are employees of Verona, the sponsor of the study. TB reports personal fees from Verona, both during the conduct of the study and outside the submitted work. DS reports personal fees from Verona during the conduct of the study. Outside the submitted work, he reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, GlaxoSmithKline, Glenmark, Menarini, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, Theravance, and Verona. The authors report no other conflicts of interest in this work.