The landscape of phosphodiesterase 3/4 (PDE3/4) inhibitors is experiencing a significant transformation in 2025, driven by advances in clinical research, new product approvals, and increased market interest. Dual PDE3/4 inhibitors are emerging as a promising therapeutic drug class with the potential to address unmet needs in the respiratory medicine, especially for patients with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and cystic fibrosis (CF), says GlobalData, a leading data and analytics company.

Filippos Maniatis, Healthcare Analyst at GlobalData, comments: “This potential is highlighted by the FDA approvals of Verona’s Ohtuvayre (ensifentrine) for COPD in June 2024 and Boehringer Ingelheim’s Jascayd (nerandomilast) for IPF in October 2025. Ohtuvayre delivers both bronchodilation and anti-inflammatory effects and continues to be studied for other respiratory diseases, including asthma and non-CF bronchiectasis. Jascayd targets PDE4B to optimize antifibrotic potency while reducing the gastrointestinal toxicity present in older PDE4 inhibitors, which can be considered an advantage compared to the current standard of care.”

The pipeline for PDE3/4 inhibitors is as interesting as the current marketed therapy landscape, with pharmaceutical companies such as GSK and Hengrui Pharma having entered agreements for the development of HRS-9821 for COPD. Other companies are also investigating drugs with a similar mechanism of action. Sino Biopharmaceutical obtained approval for the progression of TQC3721, a PDE3/4 inhibitor, to Phase III for COPD.

Kither’s KIT2014 is a peptide aimed at the increase of cyclic adenosine monophosphate levels through inhibition of PDE3/4, leading to the enhancement of the CFTR channel, which in turn results in improved mucus hydration, bronchodilation, and a reduction of neutrophil-driven inflammation, suggesting its potential in pulmonary diseases. KIT2014 is currently being investigated in CF and is in Phase 1/2a clinical trials.

Maniatis concludes: “PDE3/4 inhibitors are becoming central to respiratory and fibrotic disease therapy, offering dual bronchodilator and anti-inflammatory benefits with better safety profiles than previous treatments. Recent FDA approvals and active development pipelines confirm their potential to improve care and provide new treatment alternatives for conditions like COPD, IPF, and CF. The continued progress in both marketed and investigational agents signals a promising future for this innovative therapeutic drug class.”