ENSIFENTRINE ADDED TO TIOTROPIUM OVER 4 WEEKS PROVIDES ADDITIONAL IMPROVEMENT IN COPD QUALITY OF LIFE

Abstract

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Ensifentrine (RPL554) is an investigational, first-in-class, inhaled dual inhibitor of PDE 3 and 4 that combines bronchodilator and anti-inflammatory actions in a single compound. Results from a dose-ranging study demonstrated that twice-daily nebulised ensifentrine delivered clinically meaningful and significant improvements vs placebo (tiotropium) in lung function and quality of life when added to once-daily tiotropium over 4 weeks. This abstract reports on the effect on quality of life (St. George’s Respiratory Questionnaire for COPD patients; SGRQ-C) of ensifentrine when added to tiotropium. METHODS: This double-blind, placebo-controlled, parallel-group study enrolled COPD patients 40-80 years old, current and former smokers with a smoking history of ≥10 pack years, post-albuterol FEV1 30-70% predicted and FEV1/FVC ≤0.7. Following a 2-week run-in on tiotropium, symptomatic patients (mMRC≥2) with FEV1 30-70% predicted were randomized to receive once-daily tiotropium (Spiriva® Respimat®) plus nebulised ensifentrine (0.375, 0.75, 1.5, or 3 mg) or placebo twice daily for 4 weeks. SGRQ-C responses were collected at randomization and weeks 2 and 4. Means were calculated for the total and sub-domain scores and responder analyses for the proportion of patients that met specific minimal clinically important difference (MCID) were performed. RESULTS: Clinically meaningful and statistically significant improvements in SGRQ-C were observed over tiotropium alone (placebo), exceeding the MCID of 4 units at week 4 with the placebo-corrected change from baseline for the highest doses (1.5 mg: -4.755, p=0.0121; 3 mg: -4.047, p=0.0328). Placebo-corrected change from baseline in week 4 SGRQ-C subscales scores showed significant improvements in the impacts (1.5 mg: -4.396, p=0.0328; 3 mg: -4.981, p=0.0164) and activity (3 mg: -5.141, p=0.0466) scores. A week 4 analysis in patients that improved by at least 4, 8 and 12 units showed higher proportion of responders with at least 4 and 8 units improvement. However, in the analysis for responders with at least 12 units improvement, the difference was much more pronounced in favor of ensifentrine (0.375 mg: 24.3%, p= 0.0119; 0.75 mg: 12.9%; 1.5 mg: 13.9%; 3 mg: 20.5%) compared to placebo (tiotropium alone, 9.8%). CONCLUSIONS: Combined with a significant and clinically meaningful bronchodilator effect, ensifentrine also shows positive trends in COPD symptoms, activity and impacts related to COPD when added onto tiotropium, including a marked improvement in SGRQ-C Total Score of ≥12 units (so-called super responders) in >20% of patients treated with ensifentrine 3 mg added on to tiotropium compared to less than 10% in patients treated with placebo + tiotropium. CLINICAL IMPLICATIONS: Data demonstrates that ensifentrine added to tiotropium over 4 weeks provides additional improvement in COPD quality of life in symptomatic COPD patients. DISCLOSURES: Consultant relationship with Verona Pharma Please note: $5001 - $20000 Added 06/01/2020 by Thomas Bengtsson, source=Web Response, value=Consulting fee Employee relationship with Verona pharma Please note: >$100000 by Tara Rheault, source=Admin input, value=Stock Employee relationship with Verona Pharma Please note: >$100000 Added 05/20/2020 by Kathleen Rickard, source=Web Response, value=Salary