What is the indication for Ensifentrine (RPL554)?

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Last updated: April 23, 2025View editorial policy

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From the FDA Drug Label

The efficacy of OHTUVAYRE was evaluated in two 24-week randomized, double-blind, placebo-controlled, parallel-group clinical trials (ENHANCE-1 [NCT04535986] and ENHANCE-2 [NCT04542057]). The two trials enrolled a total of 1553 adults with moderate to severe COPD

The indication for ensifentrine is for the treatment of moderate to severe Chronic Obstructive Pulmonary Disease (COPD), as demonstrated by the results of the ENHANCE-1 and ENHANCE-2 clinical trials 1 1.

From the Research

Ensifentrine is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults, specifically as an add-on therapy to existing treatments for patients with moderate to severe COPD who are still experiencing symptoms. The medication works through a dual mechanism of action as both a phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) inhibitor, which helps relax airway smooth muscles and reduce inflammation in the lungs 2.

Key Points

  • Ensifentrine is administered as an inhalation solution via a nebulizer, with the typical dosage being 3 mg twice daily.
  • This dual inhibition mechanism differentiates it from other COPD medications that typically target only one pathway.
  • Patients should continue their other COPD medications as prescribed while using ensifentrine.
  • Common side effects include cough, headache, and shortness of breath.
  • The medication should not replace rescue inhalers for acute symptoms but rather serves as a maintenance therapy to improve overall lung function and reduce COPD exacerbations over time.

Evidence Support

The most recent and highest quality study, published in 2025, supports the use of ensifentrine in patients with COPD, demonstrating significant improvements in lung function and reductions in exacerbation rates 2. Additionally, other studies have shown that ensifentrine can provide additional benefit when added to existing treatments, such as long-acting muscarinic antagonists or long-acting beta-agonists 3, 4.

Clinical Considerations

When considering the use of ensifentrine, clinicians should take into account the patient's current treatment regimen and symptom profile. Ensifentrine may be a useful addition to existing therapies for patients with moderate to severe COPD who are still experiencing symptoms, as it has been shown to improve lung function and reduce exacerbations 5, 6. However, further research is needed to fully understand the role of ensifentrine in the treatment of COPD and to determine its optimal use in clinical practice.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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