EFFICACY OF REVEFENACIN, A LONG-ACTING MUSCARINIC ANTAGONIST FOR NEBULIZED THERAPY, IN COPD PATIENTS WITH MARKERS OF MORE SEVERE DISEASE

SESSION TITLE: Obstructive Lung Diseases 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Revefenacin (REV), a lung-selective long-acting muscarinic receptor antagonist delivered via nebulization, increased trough forced expiratory volume in 1 second (FEV1) in patients with chronic obstructive pulmonary disease (COPD) over 12 and 52 weeks. We evaluated the efficacy of once-daily REV (88 μg and 175 μg) administered by standard jet nebulizer over 12 and 52 weeks in patients with markers of more severe COPD. METHODS: Subgroup analysis was conducted over 12 weeks of 2 replicate, randomized, double-blind, placebo-controlled, parallel-group, phase 3 trials (Study 0126 [n=619], Study 0127 [n=611]), and over 52 weeks of a randomized, parallel group, active-controlled, phase 3 safety trial (Study 0128 [n=699]). The efficacy endpoint was least squares mean change from baseline in 24-hour trough FEV1 on day 85 (Studies 0126 and 0127) and day 365 (Study 0128). Four subgroups of patients at high risk of COPD exacerbations were analyzed: patients on concomitant long-acting beta agonists (LABA) or inhaled corticosteroids (ICS), patients aged >65 years (elderly), and patients classified as Global Initiative for Chronic Obstructive Lung Disease category D (GOLD D [GOLD 2011 report]). RESULTS: Analysis of pooled Study 0126 and 0127 results showed that while both REV dose levels produced statistically significant improvements in day 85 trough FEV1 versus placebo (P<0.0001), REV 175 μg produced a greater increase in trough FEV1 than REV 88 μg (148 mL vs 120 mL; P=0.088). The same efficacy trend in favor of REV 175 μg was observed across the 4 subgroups analyzed: LABA, 139 mL vs 93 mL; ICS, 131 mL vs 84 mL; elderly, 140 mL vs 123 mL; and GOLD D, 125 mL vs 81 mL. In the 52-week safety study, a similar efficacy trend in favor of REV 175 μg versus 88 μg was observed in the LABA subgroup (52 mL vs 42 mL) but not in the ICS (56 mL vs 56 mL) or elderly (36 mL vs 36 mL) subgroups. CONCLUSIONS: In key subgroups of patients with moderate to very severe COPD, the REV 175 μg dose may deliver additional benefit over the 88 μg dose regarding improvements in trough FEV1. CLINICAL IMPLICATIONS: Once-daily revefenacin over periods of up to 1 year is associated with improvements in trough FEV1 and, thus, may provide beneficial nebulized therapy for patients with COPD. DISCLOSURES: No relevant relationships by Chris Barnes, source=Web Response Employee relationship with Theravance Biopharma Please note: >$100000 Added 03/02/2018 by Glenn Crater, source=Web Response, value=Salary Employee relationship with Theravance Biopharma Please note: $20001 - $100000 Added 03/02/2018 by Glenn Crater, source=Web Response, value=Ownership interest Advisory Committee Member relationship with Mylan Inc Please note: $1001 - $5000 Added 03/02/2018 by James Donohue, source=Web Response, value=Honoraria Removed 03/02/2018 by James Donohue, source=Web Response Advisory Committee Member relationship with Sunovion Pharmaceuticals Please note: $1001 - $5000 Added 03/02/2018 by James Donohue, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Mylan Inc Please note: $1001 - $5000 Added 03/02/2018 by James Donohue, source=Web Response, value=Consulting fee Employee relationship with Theravance Biopharma Please note: >$100000 Added 03/08/2018 by Brett Haumann, source=Web Response, value=Salary Advisory Committee Member relationship with from Amphastar, AstraZeneca, Boehringer Ingelheim, Forest, M Please note: $1-$1000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Removed 06/22/2018 by Edward Kerwin, source=Web Response Consultant relationship with from Amphastar, AstraZeneca, Boehringer Ingelheim, Forest, M Please note: $1-$1000 Added 03/02/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Removed 06/22/2018 by Edward Kerwin, source=Web Response Advisory Committee Member relationship with Amphastar Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Advisory Committee Member relationship with AstraZeneca Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Consultant relationship with GSK Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Consultant relationship with Mylan Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Novartis Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Oriel Please note: $1-$1000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Consultant relationship with Pearl Please note: $1001 - $5000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Sunovion Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Honoraria Advisory Committee Member relationship with Sunovion Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Teva Please note: $1001 - $5000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Teva Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Honoraria Advisory Committee Member relationship with Theravance Please note: $5001 - $20000 Added 06/22/2018 by Edward Kerwin, source=Web Response, value=Consulting fee Employee relationship with Theravance Biopharma Please note: >$100000 Added 03/02/2018 by Edmund Moran, source=Web Response, value=Salary Employee relationship with Theravance Biopharma Please note: >$100000 Added 03/02/2018 by Edmund Moran, source=Web Response, value=Ownership interest Employee relationship with Theravance Please note: >$100000 Added 03/02/2018 by Srikanth Pendyala, source=Web Response, value=Salary