Ensifentrine is a novel inhaled, single molecule that is a potent and selective inhibitor of PDE3 and PDE4 in late-stage clinical development for treatment of patients with COPD. PDE3 and PDE4 are expressed on airway smooth muscle, inflammatory cells and bronchial epithelial cells.

Phosphodiesterase-4 (PDE₄) inhibitors are a relatively new class of medicines marketed to improve COPD. They have both bronchodilator and anti-inflammatory effects. Two currently available medicines - roflumilast and cilomilast - are taken as a tablet.

In this narrative review, we describe the general pathophysiology, inflammatory processes, and current treatment paradigms for COPD and introduce dual inhibition of phosphodiesterase (PDE) 3 and PDE4 as a novel, broadly applicable treatment strategy for patients with COPD.

PDE 4 is the primary cAMP-hydrolyzing enzyme in inflammatory and immune cells (macrophages, eosinophils, neutrophils). Inhibiting PDE 4 in these cells leads to increased cAMP levels, down-regulating the inflammatory response.

Jan 4, 2006 · The extensive in vitro, in vivo, and clinical trial study data and the established clinical beneficial effects (anti-inflammation, bronchorelaxation, pulmonary vasodilation) associated with PDE4 inhibition strongly validate targeting PDE4 for controlling COPD.

Nov 13, 2024 · Phosphodiesterase-4 (PDE4) inhibitors have been reported as an effective therapeutic strategy for inflammatory conditions, such as asthma and COPD, but their use is limited because of class-related side effects.

Sep 19, 2017 · Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE 4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013. Objectives: To evaluate the efficacy and safety of oral PDE 4 inhibitors in the management of stable COPD.

Nov 13, 2024 · Phosphodiesterase-4 (PDE4) inhibitors have been reported as an effective therapeutic strategy for inflammatory conditions, such as asthma and COPD, but their use is limited because of class-related side effects.

Currently, three companies are in the later stages of development of candidate second-generation PDE4 inhibitors for the treatment of COPD patients. The preclinical profile of one of these, BAY 19–8004, is summarized below.

PDE₄ inhibitors provided a small benefit in improving lung function and reducing the likelihood of COPD exacerbations, but they had little impact on quality of life and COPD symptoms. Side effects including diarrhoea and weight loss were common.