Ensifentrine, Novel PDE3, PDE4 Inhibitor, Improves Lung Function, QoL Regardless of COPD Severity

Ensifentrine (Ohtuvayre; Verona Pharma), the novel first-in-class dual phosphodiesterase three and phosphodiesterase 4 (PDE3, PDE4) inhibitor, was associated with significantly and clinically meaningful improvements in lung function and quality of life (QoL) in individuals with chronic obstructive pulmonary disease (COPD) regardless of disease severity, according to a new post-hoc analysis of the pivotal phase 3 ENHANCE clinical trials.¹

The findings were reported during a presentation at the CHEST 2024 Annual Meeting, October 6-9, in Boston, MA.

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Ensifentrine was approved by the US FDA in June 2024 based on the dual phase 3 global, multicenter, randomized, placebo-controlled, double-blind ENHANCE-1 and -2 studies that evaluated nebulized ensifentrine 3 mg twice daily in patients aged 40 to 80 years with symptomatic, moderate-to-severe COPD (FEV₁ 30% to 70% predicted, mMRC dyspnea score ≥2, and a ≥10 pack-year smoking history).¹ The approval was the first for an inhaled product with a novel mechanism of action for COPD in more than 20 years. Ensifentrine is the first inhaled COPD treatment that provides both bronchodilation and nonsteroidal antiinflammatory effects, according to Veronoa Pharma.²

The ENHANCE registration trials enrolled 868 participants with COPD with moderate airflow obstruction and 681 with severe airflow obstruction who were permitted to be remain on background maintenance bronchodilator therapy. The trials' primary endpoint was change from baseline to week 12 in average FEV₁ AUC(0-12h). Of secondary interest were changes at week 24 in scores for the Evaluating-Respiratory Symptoms (E-RS) total score and St George’s Respiratory Questionnaire (SGRQ) total score.¹

New analysis

In her presentation of the research at CHEST 2024, Jessica Bon MD, MS, professor of medicine, director, Airways Disease Research Center, and vice chief for research in the section of pulmonary, critical care, allergy, and immunologic diseases at Wake Forest University School of Medicine, highlighted findings from the current post-hoc pooled analysis, which further evaluated lung function, symptoms, and QoL in subgroups of patients with moderate (≤50%baseline FEV₁ <80% predicted) and severe (30% ≤ baseline FEV₁ <50% predicted) airflow obstruction.¹

FINDINGS. Bon and colleagues reported that use of ensifentrine was associated with a statistically significant improvement in FEV₁ AUC(0-12h) relative to placebo at week 12 for both the moderate and severe subgroups (P <.05). The researchers also found that treatment with ensifentrine, compared with placebo, yielded significant improvement in peak FEV₁ after 12 weeks in both groups (P <.05).¹

Treatment with ensifentrine also was associated with statistically significant improvement from baseline in symptoms reflecting QoL in both the moderate and severe airflow obstruction groups. As measured by change in E-RS total score from baseline, symptom reduction was statistically significant compared with placebo in the moderate obstruction group at study weeks 6, 12, and 14 (P <.05) and in the group with severely obstructed airflow at week 6 (P <.05).¹ The researchers reported numeric improvements in E-RS symptom scores in the severe group at weeks 12 and 14, according to the study. Both severity groups treated with ensifentrine achieved improvements in SGRQ total score compared with the placebo-treated groups at weeks 6, 12, and 14, Bon et al reported, and improvements for both groups exceeded the minimal clinically important difference for the SGRQ at weeks 6 and 24.¹

"Patients with COPD continue to suffer from impaired lung function, daily symptoms, and impaired quality of life despite available treatments,” Bon and colleagues wrote in the study abstract.¹ “Ensifentrine provides a novel mechanism of action for clinically meaningful improvements in lung function, symptoms, and quality of life regardless of COPD severity, that is complementary to existing treatment mechanisms.”¹ Ensifentrine “has the capacity to bronchodilate, reduce inflammation, augment mucociliary clearance, and reduce exacerbations in smokers and former smokers,” William Stringer, MD, professor of Medicine at the David Geffen School of Medicine at UCLA, said in a news release from Verona Pharma.³ The medication is “a remarkable addition to COPD therapy.”

References

1. Bon JM, Rheault T, Rickard KA, Dixon A, et al. Ensifentrine improved lung function, symptoms, and quality of life regardless of COPD severity. Abstract presented at CHEST 2024; October 6-9, 2024; Boston, MA. Accessed October 9, 2024. https://journal.chestnet.org/action/showPdf?pii=S0012-3692%2824%2903744-9

2. Verona Pharma announces US FDA approval of Ohtuvayre (ensifentrine). News release. Verona Pharma. June 26, 2024. Accessed October 9, 2024. https://www.veronapharma.com/news/verona-pharma-announces-us-fda-approval-of-ohtuvayre-ensifentrine/

3. Verona Pharma to present six analyses of the phase 3 enhance studies in COPD at chest 2024. News release. Verona Pharma. September 30, 2024. Accessed October 9, 2024. https://www.veronapharma.com/news/verona-pharma-to-present-six-analyses-of-the-phase-3-enhance-studies-in-copd-at-chest-2024