What are the key findings of the ENHANCE-1 and ENHANCE-2 trials for 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 primary endpoint for ENHANCE-1 and ENHANCE-2 was the change from baseline in FEV1 AUC0-12h post dose at Week 12 In both trials, OHTUVAYRE demonstrated a statistically significant improvement in FEV1 AUC0-12h compared to placebo. The mean morning trough FEV1 improvement at Week 12 relative to placebo was 35 mL (95% CI: 14,68) and 49 mL (95% CI: 19,80) in ENHANCE-1 and ENHANCE-2, respectively, In ENHANCE-1, the SGRQ responder rate (defined as an improvement in score of 4 or more as threshold) for OHTUVAYRE at Week 24 was 58.2% compared to 45.9% for placebo [Odds Ratio: 1.49; 95% CI: 1.07,2.07]. In ENHANCE-2, the SGRQ responder rate for OHTUVAYRE at Week 24 was 45.4% compared to 50.3% for placebo [Odds Ratio: 0.92; 95% CI: 0.66,1.29].

The highlights of the ENHANCE-1 and ENHANCE-2 trials for ensifentrine are:

  • Statistically significant improvement in FEV1 AUC0-12h compared to placebo in both trials.
  • Morning trough FEV1 improvement at Week 12 relative to placebo was 35 mL and 49 mL in ENHANCE-1 and ENHANCE-2, respectively.
  • SGRQ responder rate for OHTUVAYRE at Week 24 was 58.2% in ENHANCE-1 and 45.4% in ENHANCE-2. Key findings include:
  • Improved lung function as measured by FEV1 AUC0-12h.
  • Improved health-related quality of life as measured by SGRQ in ENHANCE-1. 1

From the Research

The ENHANCE-1 and ENHANCE-2 trials demonstrated that ensifentrine, a novel dual phosphodiesterase (PDE) 3 and 4 inhibitor, significantly improved lung function and reduced exacerbation risk in patients with moderate to severe COPD, as shown in the most recent study 2. The key highlights of these trials include:

  • Significant improvements in lung function, with ensifentrine showing a placebo-corrected least squares mean change from baseline in FEV1 AUC0-12 h of 92 mL in the LAMA subgroup and 74 mL in the LABA + ICS subgroup 2
  • Reductions in the rate and risk of exacerbations, with ensifentrine showing a 48% and 50% reduction in the LAMA subgroup and a 51% and 56% reduction in the LABA + ICS subgroup 2
  • Improvements in symptoms and quality of life, with ensifentrine-treated patients reporting improvements over 24 weeks 2
  • A favorable safety profile, with similar rates of adverse events between ensifentrine and placebo groups 2 The results of the ENHANCE-1 and ENHANCE-2 trials are consistent with those of other studies, which have shown that ensifentrine can provide additional benefit to existing treatments in patients with COPD, including those taking long-acting muscarinic antagonists or long-acting beta-agonists with inhaled corticosteroids 3, 4. Overall, the evidence suggests that ensifentrine is a valuable treatment option for patients with moderate to severe COPD, offering improvements in lung function, symptoms, and quality of life, as well as reductions in exacerbation risk. The use of ensifentrine can be recommended for patients with COPD who are not adequately controlled on existing therapies, based on the results of the ENHANCE-1 and ENHANCE-2 trials 2.

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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