Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study

  • Eur Respir J. 2021 Nov 18;58(5):2004240. doi: 10.1183/13993003.04240-2020.
Alyn Morice  1 ,  Jaclyn A Smith  2 ,  Lorcan McGarvey  3 ,  Surinder S Birring  4 ,  Sean M Parker  5 ,  Alice Turner  6 ,  Thomas Hummel  7 ,  Isabella Gashaw  8 ,  Lueder Fels  8 ,  Stefan Klein  8 ,  Klaus Francke  8 ,  Christian Friedrich  8
Affiliations
  • 1. Respiratory Research Group, Hull York Medical School, University of Hull, Hull, UK [email protected].
  • 2. Manchester University NHS Foundation Trust and Manchester Academic Health Science Centre, Manchester, UK.
  • 3. Wellcome Wolfson Institute of Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
  • 4. Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College Hospital, London, UK.
  • 5. North Tyneside Hospital, Northumbria Healthcare NHS Foundation Trust, North Shields, UK.
  • 6. Institute of Applied Health Research and Population Sciences, University of Birmingham, Birmingham, UK.
  • 7. Smell and Taste Clinic, Dept of Otorhinolaryngology, TU Dresden, Dresden, Germany.
  • 8. Bayer AG, Berlin, Germany.
PMID: 33986030 DOI: 10.1183/13993003.04240-2020
Abstract

Background: ATP acting via P2X3 receptors is an important mediator of refractory chronic cough (RCC). This phase 2a double-blinded crossover study assessed the safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 Receptor Antagonist, in adults with RCC attending specialist centres.

Methods: In period A, patients received placebo for 2 weeks then eliapixant 10 mg for 1 week. In period B, patients received eliapixant 50, 200 and 750 mg twice daily for 1 week per dose level. Patients were randomised 1:1 to period A-B (n=20) or B-A (n=20). The primary efficacy end-point was change in cough frequency assessed over 24 h. The primary safety end-point was frequency and severity of adverse events (AEs).

Results: 37 patients completed randomised therapy. Mean cough frequency fell by 17.4% versus baseline with placebo. Eliapixant reduced cough frequency at doses ≥50 mg (reduction versus placebo at 750 mg: 25% (90% CI 11.5-36.5%); p=0.002). Doses ≥50 mg also significantly reduced cough severity. AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 41-49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with placebo and 5-21% with eliapixant; all were mild.

Conclusions: Selective P2X3 antagonism with eliapixant significantly reduced cough frequency and severity, confirming this as a viable therapeutic pathway for RCC. Taste-related side-effects were lower at therapeutic doses than with the less selective P2X3 antagonist gefapixant. Selective P2X3 antagonism appears to be a novel therapeutic approach for RCC.

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