B24-10 Earlier Onset of Bronchodilation With Revefenacin: New Analyses From Phase 3 COPD Trials

Background Revefenacin (REV), a once-daily nebulized long-acting muscarinic antagonist, is approved for maintenance therapy in COPD. Onset data at Day 84 from a prespecified 24-hour spirometry sub-study nested within the revefenacin Phase 3 registrational program has been previously reported. Herein, we report onset data at Day 1 from the same spirometry sub-study, as well as from the intent-to-treat (ITT) population in the Phase 3 program overall. Methods Using individual and pooled ITT data from two Phase 3 studies (0126, 0127), least-squares (LS) mean change from baseline FEV1 was calculated at early post-dose timepoints on Day 1. Models incorporated treatment, smoking status, reversibility stratum, LABA use, sex, and age, with baseline FEV1 as a covariate. Data were compared with results from the published 24-hour spirometry sub-study assessing area under the curve. Results On Day 1 in the individual Phase 3 ITT populations, LS mean FEV1 improvements with REV first exceeded 100 mL above baseline at 30 minutes post-dose. Pooled ITT Day 1 analysis showed LS mean increases of 90 mL at 15 minutes and 132 mL at 30 minutes. The Day 1 24-hour sub-study population displayed significant bronchodilation within 15 minutes: mean FEV1 improvement of 116 mL from baseline and LS mean difference vs. placebo of 145 mL (95% CI: 99, 191; p<0.001). Pooled ITT Day 1 analysis similarly showed a placebo-corrected mean difference of 114 mL at 15 minutes (95% CI: 94, 134), exceeding the minimum clinically important difference with >92% confidence. Baseline demographics in the sub-study and ITT populations were comparable, supporting generalizability. Conclusions These new analyses confirm that revefenacin provides clinically significant bronchodilation at 30 minutes following an initial dose with meaningful effects observed as early as 15 minutes. These effects on Day 1 are consistent across the Phase 3 populations. The findings extend previously reported onset data for revefenacin following repeat dosing.