Treatment with nebulized ensifentrine resulted in significant improvements in lung function and reduced the rate and risk of chronic obstructive pulmonary disease (COPD) exacerbations, according to topline results from a phase 3 trial.

Ensifentrine is a first-in-class, dual phosphodiesterase (PDE) 3 and 4 inhibitor with combined bronchodilator and anti-inflammatory actions. The ENHANCE-1 trial (ClinicalTrials.gov Identifier: NCT04535986) evaluated the efficacy and safety of nebulized ensifentrine as monotherapy or as an add-on to a long-acting muscarinic antagonist (LAMA) or a long-acting beta-agonist (LABA) in patients with moderate to severe COPD. Patients were randomly assigned to receive either nebulized ensifentrine 3mg or placebo twice a day for 24 or 48 weeks. 

The primary endpoint was the change from baseline of average forced expiratory volume in 1 second (FEV1) area under the curve (AUC) 0 to 12 hours post dose at week 12. Secondary endpoints included peak and morning trough FEV1, COPD symptoms and health-related quality of life (St. George’s Respiratory Questionnaire [SGRQ]) at 24 weeks.

Results showed that treatment with ensifentrine met the primary endpoint demonstrating a statistically significant and clinically meaningful improvement in lung function (placebo-corrected change from baseline in FEV1 AUC0-12 post dose of 87mL; P <.0001). Improvements in secondary endpoints were also observed with an increase in peak FEV1 of 147mL at 0 to 4 hours post dose (P <.0001) and an increase in morning trough FEV1 of 35mL (P =.0421) at week 12.

Compared with placebo, patients treated with ensifentrine were found to have statistically significant improvements in daily symptoms as measured by the Evaluating-Respiratory Symptoms (E-RS) total score at week 24. Statistically significant improvements in quality of life (as measured by SGRQ total score) were also observed in the ensifentrine arm compared with placebo.

Additionally, treatment with ensifentrine was associated with a 36% reduction in the rate of moderate to severe COPD exacerbations (P =.0505) and significantly reduced the risk of a moderate to severe exacerbation (as measured by time to first exacerbation) by 38% (P =.0378), when compared with placebo. 

Commenting on the findings, Antonio Anzueto, MD, Professor of Medicine and Section, Chief of Pulmonary at South Texas Veterans Healthcare System, said: “These exciting results demonstrate ensifentrine’s potential to become a first-in-class bronchodilator and nonsteroidal anti-inflammatory therapy for COPD. Combined with the significant improvements in lung function, symptom and quality of life measures, as well as the favorable safety profile, these data confirm ensifentrine’s potential to change the treatment paradigm for COPD patients.”

Verona Pharma previously announced positive topline results for nebulized ensifentrine in the ENHANCE-2 trial. Additional information from both ENHANCE-1 and ENHANCE-2 will be released at upcoming scientific conferences.

The Company plans to submit a New Drug Application to the Food and Drug Administration in the first half of 2023. 

Reference

Verona Pharma announces ensifentrine meets primary and key secondary endpoints in phase 3 ENHANCE-1 trial for COPD. News release. Verona Pharma. Accessed December 20, 2022. https://www.veronapharma.com/media/verona-pharma-announces-ensifentrine-meets-primary-and-key.