Ensifentrine: First Novel-Mechanism COPD Drug in Over a Decade, Explained

Ensifentrine, an inhaled dual PDE3/PDE4 inhibitor given as 3 mg twice daily by nebulisation, received FDA approval in 2024 as the first COPD drug with a new mechanism in more than ten years. It raises cAMP, producing bronchodilation and anti-inflammatory effects, and is positioned as add-on therapy to LAMA/LABA/ICS. In the ENHANCE 1 and 2 trials of about 700 patients each, FEV1 improved by 87 and 94 mL, while the exacerbation endpoint in ENHANCE 2 missed significance owing to high placebo-group dropout.