Inhaled Therapy with Ensifentrine Significantly may Reduce COPD Exacerbations, unravels research

A new study published in the CHEST journal found that ensifentrine, an innovative inhaled therapy, significantly reduces the rate and risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). The findings from a pooled analysis of two phase 3 clinical trials highlighted the drug’s potential to improve the quality of life for COPD patients with serious exacerbations.

COPD exacerbations are sudden worsening of symptoms which can lead to irreversible lung damage, increased hospitalization rates, and a decline in overall health. Medications that effectively reduce these exacerbations remain an unmet need, as exacerbations tend to increase the risk of further episodes and diminish the patients' quality of life.

Ensifentrine is a first-in-class dual inhibitor of phosphodiesterase (PDE) 3 and 4, offering both bronchodilatory and nonsteroidal anti-inflammatory benefits. The drug was evaluated in two large clinical trials (ENHANCE-1 and ENHANCE-2) which enrolled symptomatic patients aged 40 to 80 with moderate to severe COPD. The participants received either 3 mg of ensifentrine twice daily or a placebo over 24 weeks, with the study assessing the impact of drug on exacerbation rates and the time to first exacerbation.

The pooled analysis included a total of 975 patients treated with ensifentrine and 574 who received placebo. Also, 62% of participants were also using either long-acting muscarinic antagonists (LAMA) or long-acting β2-agonists (LABA), while 18% were on inhaled corticosteroids.

These results showed a 41% reduction in the rate of moderate to severe exacerbations among patients taking ensifentrine when compared to the placebo group (rate ratio: 0.59, 95% confidence interval [CI]: 0.43-0.80; p < .001). Similarly, the risk of experiencing an exacerbation was also reduced by 41% (hazard ratio: 0.59, 95% CI: 0.44-0.81; p < .001).

The study further revealed that the benefits of ensifentrine extended across multiple patient subgroups, regardless of age, sex, race, disease severity, history of exacerbations, eosinophil count, or background COPD medication use.

This data suggested that ensifentrine may help delay progression of patients from infrequent exacerbators (Global Initiative for Chronic Obstructive Lung Disease Group B) to frequent exacerbators (Group E), indicating a potential role in slowing disease progression. Overall, these findings underline the potential of ensifentrine as a strong addition to COPD management, addressing the urgent need for therapies that reduce exacerbation rates and improve long-term outcomes.

Reference:

Sciurba, F. C., Christenson, S. A., Rheault, T., Bengtsson, T., Rickard, K., & Barjaktarevic, I. Z. (2025). Effect of dual phosphodiesterase 3 and 4 inhibitor ensifentrine on exacerbation rate and risk in patients with moderate to severe COPD. Chest, 167(2), 425–435. https://doi.org/10.1016/j.chest.2024.07.168