What are the results of the ENHANCE 1 and 2 trials on ensifentrine (RPL554)?

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. Table 2 Least Squares (LS) Mean Change from Baseline in FEV1 AUC0-12h (mL) at Week 12 in ENHANCE-1 and ENHANCE-2 ENHANCE-1: OHTUVAYRE(N=479) LS Mean (95% CI) 61(25,97) ENHANCE-2: OHTUVAYRE(N=499) LS Mean (95% CI) 48(30,66) 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

The ENHANCE-1 and ENHANCE-2 trials were two 24-week randomized, double-blind, placebo-controlled, parallel-group clinical trials that evaluated the efficacy of ensifentrine (OHTUVAYRE).

• The primary endpoint was the change from baseline in FEV1 AUC0-12h post dose at Week 12.
• In both trials, ensifentrine demonstrated a statistically significant improvement in FEV1 AUC0-12h compared to placebo.
• The LS Mean Change from Baseline in FEV1 AUC0-12h was 61 mL (95% CI: 25,97) in ENHANCE-1 and 48 mL (95% CI: 30,66) in ENHANCE-2.
• The mean morning trough FEV1 improvement at Week 12 relative to placebo was 35 mL (95% CI: 14,68) in ENHANCE-1 and 49 mL (95% CI: 19,80) in ENHANCE-2 1

From the Research

Ensifentrine, a novel dual phosphodiesterase (PDE) 3 and 4 inhibitor, has been shown to be effective in treating chronic obstructive pulmonary disease (COPD) in the ENHANCE-1 and ENHANCE-2 trials, with significant improvements in lung function, symptoms, and quality of life, as well as reductions in COPD exacerbations 2.

Key Findings

• The ENHANCE-1 and ENHANCE-2 trials were Phase 3, randomized, double-blind, placebo-controlled studies that evaluated nebulized ensifentrine 3 mg twice daily over 24 weeks in symptomatic COPD patients 2.
• Ensifentrine significantly improved lung function, with increases in FEV1 of 87 mL in ENHANCE-1 and 94 mL in ENHANCE-2 compared to placebo 2.
• Both studies demonstrated significant reductions in COPD exacerbations, with a rate ratio of 0.64 in ENHANCE-1 and 0.57 in ENHANCE-2, and improvements in quality of life measures 2.
• Ensifentrine's dual mechanism of action provides both bronchodilation and anti-inflammatory effects, making it particularly valuable for COPD patients who remain symptomatic despite standard therapies 2.

Safety and Efficacy

• The medication was generally well-tolerated, with similar adverse event profiles between treatment and placebo groups 2.
• A pooled post-hoc analysis of the ENHANCE-1 and ENHANCE-2 trials found that ensifentrine improved lung function and reduced exacerbations in patients taking long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS) 3.
• A systematic review and meta-analysis of randomized controlled trials found that ensifentrine significantly improved lung function, symptoms, and quality of life in COPD patients, with a stable safety profile 4, 5.

Clinical Implications

• Ensifentrine is a valuable treatment option for COPD patients, particularly those who remain symptomatic despite standard therapies, due to its dual mechanism of action and significant improvements in lung function, symptoms, and quality of life 2, 3, 4, 5.