Nebulized ensifentrine significantly improves lung function and reduces COPD exacerbations: Phase 3 trial results

USA: Nebulization with ensifentrine significantly improved lung function and reduced the risk and rate of COPD (chronic obstructive pulmonary disease) exacerbations, topline results from Phase 3 ENHANCE-1 Trial for COPD reveal.

Ensifentrine is a first-in-class, selective dual inhibitor of the enzymes phosphodiesterase 3 and 4, combining bronchodilator and non-steroidal anti-inflammatory activities in one compound.

Highlights

• Study population (n=763):

° Subject demographics and disease characteristics were well balanced between treatment groups.

° Approximately 66% of subjects received background COPD therapy, either a long-acting muscarinic antagonist ("LAMA") or a long-acting beta-agonist ("LABA"). Additionally, approximately 21% of all subjects received inhaled corticosteroids ("ICS") with concomitant LAMA or LABA.

Primary endpoint met (FEV1* AUC 0-12 hr):

° Placebo corrected, change from baseline in FEV1 area under the curve 0-12 hours post dose at week 12 was 87 mL (p<0.0001) for ensifentrine.

° Demonstrated consistent improvements in all subgroups including gender, age, smoking status, COPD severity, background medication, ICS use, chronic bronchitis, FEV1 reversibility and geographic region.

• Key secondary endpoints of lung function, symptoms and quality of life measures met:

° Placebo corrected, increase in peak FEV1 of 147 mL (p<0.0001) 0-4 hours post dose at week 12.

° Daily symptoms as measured by E-RS** Total Score in the ensifentrine group improved from baseline to greater than the minimal clinically important difference ("MCID") of -2 units with a statistically significant improvement compared to placebo at week 24. Improvements in symptoms were early and sustained with statistical significance versus placebo at weeks 6, 12 and 24.

° Quality of Life ("QOL") as measured by SGRQ** Total Score in the ensifentrine group improved from baseline to greater than the MCID of -4 units with a statistically significant improvement compared to placebo at week 24. Improvements in QOL were early and sustained with statistical significance versus placebo at weeks 6, 12 and 24.

° Placebo corrected, increase in morning trough FEV1 of 35 mL (p=0.0421) at week 12, supporting twice daily dosing regimen.

Exacerbation rate and risk reduced:

° Subjects receiving ensifentrine demonstrated a 36% reduction in the rate of moderate to severe COPD exacerbations over 24 weeks (p=0.0505) compared to those receiving placebo.

° Treatment with ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 38% (p=0.0378).

°Pooled exacerbation data from ENHANCE-1 and ENHANCE-2, ensifentrine demonstrated a 40% reduction in the rate of moderate to severe COPD exacerbations over 24 weeks (p=0.0012) compared to those receiving placebo. Additionally, ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 41% (p=0.0008).

Favorable safety profile:

Ensifentrine was well-tolerated with very few events occurring in more than 1% of subjects and greater than placebo over 24 and 48 weeks.

*FEV1: Forced Expiratory Volume in one second, a standard measure of lung function

**E-RS, Evaluating Respiratory Symptoms, and SGRQ, St. George's Respiratory Questionnaire, are validated patient reported outcome tools

Antonio Anzueto, MD, Professor of Medicine and Section, Chief of Pulmonary at South Texas Veterans Healthcare System, commented: "These exciting results demonstrate ensifentrine's potential to become a first-in-class bronchodilator and non-steroidal anti-inflammatory therapy for COPD. The 36% reduction in the rate of exacerbations observed over 24 weeks in symptomatic patients is impressive. 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."

David Zaccardelli, Pharm. D., Verona Pharma's President and Chief Executive Officer, said: "We are very pleased by the successful outcome of our Phase 3 ENHANCE-1 study, bringing us another step closer to providing a much needed novel therapy for COPD patients. The totality of the ENHANCE data including improvements in lung function, symptoms, quality of life measures and reduction in exacerbations, coupled with the consistent, favorable safety profile, support our belief that ensifentrine will change the treatment paradigm for COPD. We plan to submit a New Drug Application to the US Food and Drug Administration in the first half of 2023. We would like to thank all the patients and investigators for their participation in the ENHANCE program and we look forward to keeping you updated on our progress."