Ensifentrine, an FDA-approved COPD medication, has shown early promise in treating pulmonary hypertension complications in COPD patients, with research demonstrating modest improvements in lung pressure, exercise capacity, and breathlessness over six months without significant adverse effects.
- Ensifentrine is a dual phosphodiesterase 3/4 inhibitor approved by the FDA in 2024 for moderate-to-severe COPD treatment.
- Pulmonary hypertension complicates advanced COPD in an estimated 34% to 64% of patients, with no currently approved specific treatment.
- Six-month study results showed mean pulmonary artery pressure fell 1.6 mmHg, pulmonary vascular resistance decreased, and six-minute walk distance improved by 31 meters.
- The treatment did not provoke exacerbations, worsen oxygenation, or cause significant adverse events in the studied patients.
- Researchers call for multicenter randomized controlled trials to confirm findings and clarify whether improvements result from direct vascular action, improved airflow, or both.
Ensifentrine, a COPD treatment approved by the U.S. Food and Drug Administration (FDA) in 2024 for moderate-to-severe COPD, has shown promise in treating pulmonary hypertension (PH) symptoms associated with the condition.
The research article, “A Breath of Life Beyond Bronchodilation: Early Data on Hemodynamic and Functional Outcomes With Ensifentrine Nebulization in Severe COPD-Associated Pulmonary Hypertension,” was published in The Open Respiratory Medicine Journal.
The researchers found that nebulized ensifentrine, an inhaled, dual phosphodiesterase 3/4 inhibitor, was associated with modest but consistent improvements in pulmonary hemodynamics, exercise capacity and patient-reported breathlessness overs six months in patients with severe, COPD-associated PH. The treatment also did not provoke exacerbations, worsen oxygenation or lead to significant adverse events.
Pulmonary hypertension complicates advance COPD in an estimated 34% to 64% of patients. According to researchers, it is caused by chronic hypoxic vasoconstriction and progressive remodeling of the pulmonary vasculature, which results in increased right ventricular afterload, reduced exercise tolerance and lower survival rates. There is currently no approved treatment specifically for COPD-associated PH.
The research team at CentraCare Health System in Minnesota conducted a single-center, retrospective chart review of patients with confirmed pre-capillary PH who received nebulized ensifentrine at 3 mg twice daily between September 2024 and May 2025.
Though only five patients were reviewed, the researchers found the following changes after six months:
- Mean pulmonary artery pressure fell by 1.6 mmHg
- Pulmonary vascular resistance fell from 9.5 to 8.5 Wood units
- Cardiac index rose marginally from 2.5 to 2.6 L/min/m2
- Six-minute walk distance improved by a mean of 31 meters
- Patient-reported dyspnea improved on both the Medical Research Council scale and the COPD Assessment Test
The researchers wrote that with only five patients, no control group and an inherently retrospective design, the results are presented “explicitly as hypothesis generating.” They said that while the observed improvements cannot be attributed to ensifentrine with confidence, they believe the evidence is enough to justify a formal prospective investigation.
“The authors call for multicenter, randomized, controlled trials with pre-specified hemodynamic and functional co-primary endpoints, as well as mechanistic sub-studies using cardiac magnetic resonance imaging and gas exchange assessment to clarify whether the observed effects are driven by direct vascular action, improved airflow or both,” according to a press release by Bentham Science Publishers.
