Ensifentrine improves outcomes in both moderate, severe COPD

Key takeaways:

• Patients with moderate or severe COPD experienced improvements with 3 mg of twice-daily ensifentrine.
• Study outcomes included peak FEV₁, transition dyspnea index score and Evaluating-Respiratory Symptoms score.

BOSTON — Lung function, symptoms and quality of life improved with receipt of ensifentrine in both adults with moderate COPD and adults with severe COPD, according to data presented at the CHEST Annual Meeting.

“Ensifentrine provides a novel mechanism of action for clinically meaningful improvements in lung function, symptoms and quality of life regardless of COPD severity,” Jessica M. Bon, MD, MS, professor of medicine, director of the Airways Disease Research Center and vice chief for research of the section of pulmonary, critical care, allergy and immunologic diseases at Wake Forest University School of Medicine, wrote on her presentation slide.

As Healio previously reported, adults with moderate to severe COPD who were symptomatic and smoked a minimum of 10 pack-years receiving 3 mg of twice-daily nebulized ensifentrine (Ohtuvayre, Verona Pharma) showed improved measures of lung function, quality of life and exacerbation rate over 12 or 24 weeks in the phase 3 ENHANCE-1 and ENHANCE-2 trials.

Pooling together the trials, Bon and colleagues divided the population into those with moderate airflow obstruction (50% ≤ baseline FEV₁ < 80% predicted; n = 868) and those with severe airflow obstruction (30% ≤ baseline FEV₁ < 50% predicted; n = 681) to determine if ensifentrine’s impact changes based on airflow obstruction/COPD severity.

Notably, the FDA approved ensifentrine for treating adults with COPD this past June.

In the moderate COPD group, 561 patients received ensifentrine and 307 received placebo, and these numbers were slightly lower in the severe COPD group, with 414 patients receiving ensifentrine and 267 patients receiving placebo, according to the abstract.

Among patients with moderate COPD, researchers observed a significant increase in FEV₁ area under the curve over 12 hours with ensifentrine vs. placebo (least-squares mean change at week 12 from baseline, +111 mL; P < .05). A similar outcome favoring ensifentrine was reported in the severe COPD cohort (least-squares mean change, +61 mL; P < .05).

Additionally, peak FEV₁ at week 12 was significantly higher in patients receiving ensifentrine vs. placebo in the moderate COPD cohort (least-squares mean change from baseline, +170 mL; P < .05), as well as in the severe COPD cohort (least-squares mean change, +114 mL; P < .05).

In terms of symptoms, researchers reported that patients with moderate COPD had more improvement in transition dyspnea index (TDI) scores at the three assessed periods if they had been taking ensifentrine rather than placebo (least-squares mean: week 6, 1.4 vs. 0.8; week 12, 1.5 vs. 0.6; week 24, 2 vs. 0.9). This was also the case for patients with severe COPD (least-squares mean: week 6, 1.2 vs. 0.4; week 12, 1.4 vs. 0.6; week 24, 1.8 vs. 0.9).

The Evaluating-Respiratory Symptoms (E-RS) total score was significantly better in the ensifentrine group vs. the placebo group among patients with moderate COPD at each follow-up (least-squares mean: week 6, –2 vs. –0.9; week 12, –2.5 vs. –1.1; week 24, –2.4 vs. –1.5), according to the presentation.

Among those with severe COPD, significant improvement with ensifentrine was only found at week 6 (least-squares mean, –1.8 vs. –0.8), but at weeks 12 and 24, those receiving ensifentrine did have significantly larger decreases in this score than those receiving placebo.

Lastly, patients receiving ensifentrine in the moderate COPD cohort and the severe COPD cohort had more improved quality of life than patients receiving placebo via changes in baseline St. George’s Respiratory Questionnaire total score at each time point.

According to the presentation, this change met/surpassed the minimal clinically important difference at all three points in the moderate COPD cohort and at weeks 6 and 24 in the severe COPD cohort.

“[These findings are] especially important given that as patients lung function declines over time, additional pharmacotherapeutic mechanisms to maximize treatment effects are needed,” Bon wrote on a presentation slide.