PRELIMINARY ESTIMATES OF OFF-TREATMENT DURABILITY OF GEFAPIXANT ACROSS TWO PHASE 3 STUDIES OF PARTICIPANTS WITH REFRACTORY OR UNEXPLAINED CHRONIC COUGH

Abstract

TOPIC: Respiratory Care TYPE: Original Investigations PURPOSE: In two phase 3, randomized, placebo-controlled trials (COUGH-1, NCT03449134; COUGH‑2, NCT03449147), 52 weeks of twice-daily (BID) treatment with gefapixant 45 mg, a P2X3-receptor antagonist, significantly reduced patient-reported cough severity and improved cough-related quality of life in participants with refractory or unexplained chronic cough (RCC and UCC, respectively). This exploratory, observational study in a subset of participants from COUGH-1 and COUGH-2 evaluated the 3-month off-treatment durability of gefapixant in participants with a treatment response after 1 year of treatment. METHODS: Participants from a subset of study sites in select countries who completed 1 year of treatment in COUGH-1 or COUGH-2 and were ≥80% compliant with the completion of patient-reported outcome entries and ≥80% adherent to study intervention through the main and extension study periods were eligible. Responders at 52 weeks from baseline were defined as those who achieved a ≥30-mm reduction on the cough severity visual analog scale (VAS), a ≥1.3-point increase on the Leicester Cough Questionnaire (LCQ), or a ≥1.3- or ≥2.7-point reduction on the Cough Severity Diary (CSD). Treatment durability was assessed as the proportion of responders in each treatment group (ie, placebo, gefapixant 15 mg BID, or gefapixant 45 mg BID) after the 3-month off-treatment phase (Week 64). RESULTS: Of 163 participants enrolled in the off-treatment study, 58, 55, and 50 had received placebo, gefapixant 15 mg, or gefapixant 45 mg, respectively, in COUGH-1 or COUGH-2. Participant characteristics were generally comparable with the overall study population and across intervention groups. At Week 52, 52%, 43%, and 74% of participants were VAS responders in the placebo, gefapixant 15 mg, and gefapixant 45 mg groups, respectively, with 91%, 67%, and 86% of responders demonstrating a response at Week 64. At Week 52, 63%, 83%, and 81% of participants were LCQ responders, respectively, with 88%, 87%, and 80% of responders demonstrating a response at Week 64. For the CSD cutoff of ≥1.3-point reduction from baseline, 67%, 77%, and 91% of participants were responders at Week 52, respectively, with 93%, 78%, and 92% of responders demonstrating a response at Week 64. For the CSD cutoff of ≥2.7-point reduction, 44%, 43%, and 79% of participants were responders at Week 52, respectively, with 90%, 80%, and 71% of responders demonstrating a response at Week 64. CONCLUSIONS: A high proportion of participants with RCC or UCC who demonstrated a treatment response after 52 weeks of study intervention demonstrated a response after a 3-month off-treatment period, with consistent results across VAS, LCQ, and CSD outcomes. CLINICAL IMPLICATIONS: This exploratory study suggests treatment with gefapixant 45 mg for 52 weeks may result in some durability of treatment effect. Further data will help inform durability after treatment cessation. DISCLOSURES: Advisory Committee Member relationship with Merck Please note: $1001 - $5000 by Surinder Birring, source=Web Response, value=Consulting fee Consultant relationship with Merck Please note: 2017-2021 Added 04/28/2021 by Peter Dicpinigaitis, source=Web Response, value=Consulting fee Employee No relevant relationships by Lorcan McGarvey, source=Web Response Advisory Committee Member relationship with Merck Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bellus Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bayer Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Sanofi Please note: $5001 - $20000 by Alyn Morice, source=Web Response, value=Consulting fee Employee relationship with MSD Please note: 11/2016 to current Added 05/06/2021 by David Muccino, source=Web Response, value=Salary Employee relationship with Merck Sharp & Dohme Corp. Please note: May 1995 - present Added 04/30/2021 by Allison Nguyen, source=Web Response, value=Salary Advisory Committee Member relationship with GSK Please note: $1001 - $5000 by Ian Pavord, source=Web Response, value=Consulting fee Employee relationship with Merck & Co., Inc. Please note: 7 years Added 04/30/2021 by Jonathan Schelfhout, source=Web Response, value=Salary Scientific Medical Advisor relationship with Merck Please note: $1001 - $5000 by Jaclyn Smith, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Vitalograph Ltd Please note: $5001 - $20000 by Jaclyn Smith, source=Web Response, value=Grant/Research Support Grant Funding relationship with Merck Please note: 2020-2022 Added 05/01/2021 by Jaclyn Smith, source=Web Response, value=Grant/Research Support Employee relationship with Merck & Co, Inc Please note: 2019 to Present Added 04/30/2021 by Ping Xu, source=Web Response, value=Salary