Ensifentrine reduces copd symptoms and rescue medication use over 24 weeks in two phase 3 trials in symptomatic patients with moderate to severe copd

SESSION TITLE: Latest Advances in Management of Obstructive Lung Disease SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/09/2023 12:00 pm - 12:45 pm PURPOSE: Ensifentrine is a first-in-class, inhaled dual inhibitor of phosphodiesterase (PDE)3 and PDE4 with demonstrated bronchodilation and anti-inflammatory effects. This abstract reports on ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057), two Phase 3 trials of nebulized ensifentrine in COPD. METHODS: Two Phase 3, 24-week, multi-center, randomized, double-blind, placebo-controlled trials were performed to evaluate nebulized ensifentrine-3mg twice-daily (BID) compared to placebo in subjects aged 40-80 years with symptomatic moderate to severe COPD (post-bronchodilator FEV1 30–70% predicted, FEV1/FVC ratio <0.7, ≥2 mMRC, and smoking history ≥10 pack-years. Stable background maintenance bronchodilator medication was permitted (LABA or LAMA, ±ICS). Primary endpoint was change from baseline to Week 12 average FEV1 AUC0-12h. Evaluating-Respiratory Symptoms (E-RS Total Score) and rescue medication use were collected via daily eDiary. Symptom endpoints included the change from baseline in E-RS Total Score, weekly rescue medication use (mean daily puffs over a week) and Transitional Dyspnea Index (TDI) at Weeks 6, 12 and 24. RESULTS: In ENHANCE-1 and ENHANCE-2 there were 760 (ensifentrine n=477, placebo n=283) and 789 (ensifentrine n=498, placebo n=291) treated subjects, respectively ENHANCE-1 & ENHANCE-2 had respectively 42% and 52% female subjects;57% & 55% current smokers; 69% and 55% of subjects taking background long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA), including 18% and 15% taking inhaled corticosteroid (ICS) with their bronchodilator. Baseline E-RS Total score, Baseline Dyspnea Index and rescue medication use was similar between ensifentrine and placebo-treated subjects. Treatment with ensifentrine resulted in consistent improvements from baseline in E-RS Total Score, TDI and rescue medication use vs placebo at Weeks 6, 12 and 24. At Week 24, the E-RS Total Score (ENHANCE-1: -1.0 [95%CI: -1.7, -0.2]; ENHANCE-2: -0.6 [95%CI: -1.4, 0.2]), TDI (ENHANCE-1: 1.0 [95%CI: 0.6, 1.5]; ENHANCE-2: 0.9 [95%CI: 0.4, 1.4]) and weekly rescue medication use (ENHANCE-1: -0.45 [95%CI: -0.70, -0.20]; ENHANCE-2: -0.14 [95%CI: -0.41, 0.14] were improved vs placebo. CONCLUSIONS: Over 24 weeks, the ENHANCE trials demonstrated consistent improvements in COPD symptoms in ensifentrine-treated subjects compared to placebo, including statistically significant improvements in dyspnea at all weeks, and reduction in daily rescue medication use. In these studies, ensifentrine has demonstrated early and sustained, clinically meaningful improvements in COPD symptoms in a broad moderate to severe COPD population, with >50% subjects taking background COPD therapy. CLINICAL IMPLICATIONS: Ensifentrine demonstrated early and sustained, clinically meaningful improvements in COPD symptoms in a broad moderate to severe COPD population, with >50% subjects taking background COPD therapy. DISCLOSURES: Consultant relationship with Verona Pharma Please note: $5001 - $20000 by Thomas Bengtsson, value=Consulting fee Employee relationship with Verona pharma Please note: >$100000 by Tara Rheault, value=Stock Employee relationship with Verona Pharma Plc Please note: >$100000 by Kathleen Rickard, value=Salary Grant Support relationship with Gala Therapeutics, Inc Please note: 9/2018-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with Pulmonx Please note: 9/2014-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with Nuvaira, Inc Please note: 5/2018-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with PCORI Please note: 6/2019-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with PneumRx Please note: 10/2012 by Frank Sciurba, value=Grant/Research Support Grant Support relationship with American Lung Assosciation Please note: 7/2021-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with Gala Therapeutics, Inc Please note: 9/2019-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with PneumRx Please note: 10/2013-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with ResMed Corp Please note: 8/2018-Present by Frank Sciurba, value=Grant/Research Support Grant Support relationship with Regeneron/Sanofi US Services, Inc Please note: 5/2018-Present Added 04/10/2023 by Frank Sciurba, value=Grant/Research Support Advisory Committee Member relationship with Glaxosmithkline (GSK) Please note: 2/2023 Added 04/10/2023 by Frank Sciurba, source=Web Response, value=Honoraria Grant Support relationship with Verona Pharma Please note: 4/2019-Present Added 04/10/2023 by Frank Sciurba, source=Web Response, value=Grant/Research Support Grant Support relationship with AstraZeneca Please note: 2/2020-Present Added 04/10/2023 by Frank Sciurba, source=Web Response, value=Grant/Research Support