What trials involve ensifentrine (RPL554)?

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Last updated: April 2, 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 ENHANCE-1 enrolled a total of 763 patients randomized 5:3 to receive 3 mg of OHTUVAYRE administered by oral inhalation via standard jet nebulizer such as PARI LC Sprint® [see Description (11)], or placebo. ENHANCE-2 enrolled a total of 790 patients randomized 5:3 to receive 3 mg of OHTUVAYRE twice daily administered by oral inhalation via a standard jet nebulizer such as PARI LC Sprint [see Description (11)] or placebo.

The trials that involve ensifentrine are:

  • ENHANCE-1 [NCT04535986]
  • ENHANCE-2 [NCT04542057] 1

From the Research

Ensifentrine has been evaluated in several clinical trials, most notably the Phase 3 ENHANCE program, which includes two studies (ENHANCE-1 and ENHANCE-2) that demonstrated its efficacy and safety in patients with chronic obstructive pulmonary disease (COPD) 2.

Key Findings

  • The ENHANCE trials showed that ensifentrine, a dual phosphodiesterase (PDE) 3 and 4 inhibitor delivered via nebulizer, significantly improved lung function and reduced symptoms in COPD patients.
  • The typical dosage studied was 3 mg administered twice daily via nebulizer.
  • Ensifentrine has also been investigated in earlier phase trials for cystic fibrosis and asthma.
  • The medication works through a novel mechanism that combines bronchodilation and anti-inflammatory effects by inhibiting both PDE3 and PDE4 enzymes, making it potentially valuable for patients who don't respond adequately to current standard treatments.

Trial Overview

  • The ENHANCE-1 and ENHANCE-2 trials were randomized, double-blind, placebo-controlled, multicenter Phase III trials that assessed the efficacy and safety of ensifentrine in patients with moderate to severe COPD 2.
  • A pooled analysis of the ENHANCE trials demonstrated that ensifentrine reduced the rate and risk of moderate to severe exacerbations compared to placebo 3.
  • Ensifentrine has also been shown to improve symptoms and quality of life in patients with COPD, with a notable effect on dyspnea 4.

Recommendations

  • Based on the most recent and highest quality evidence, ensifentrine is a promising treatment option for patients with COPD, particularly those who do not respond adequately to current standard treatments 2, 3.
  • Ensifentrine may be considered as a monotherapy or as an add-on to existing treatments, and its efficacy and safety have been demonstrated in patients with moderate to severe COPD.

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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