Ensifentrine meets primary and key secondary endpoints in phase III ENHANCE-1 trial for COPD.- Verona Pharma Plc

In addition, ensifentrine substantially reduced the rate and risk of COPD exacerbations. Ensifentrine was well tolerated over 24 and 48 weeks.

Highlights : Study population (n=763) : i. Subject demographics and disease characteristics were well balanced between treatment groups. ii. 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) : i. 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. ii. demonstrated consistent improvements in all subgroups including gender, age, smoking status, copd severity, background medication, ics use, chronic bronchitis, fev1 reversibility and geographic region.></0.0001)>

Key secondary endpoints of lung function, symptoms and quality of life measures met : i. Placebo corrected, increase in peak FEV1 (Forced Expiratory Volume in one second, a standard measure of lung function) of 147 mL (p<0.0001) 0-4 hours post dose at week 12. ii. daily symptoms as measured by e-rs (evaluating respiratory symptoms, and sgrq, st. george’s respiratory questionnaire, are validated patient reported outcome tool). 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. iii. 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. iv. 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 : i. 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. ii. 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). iii. 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.</0.0001)>