Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: A randomised, placebo-controlled, crossover phase 2a study
Morice, Alyn; Smith, Jaclyn A.; McGarvey, Lorcan; Birring, Surinder S.; Parker, Sean M.; Turner, Alice; Hummel, Thomas; Gashaw, Isabella; Fels, Lueder; Klein, Stefan; Francke, Klaus; Friedrich, Christian
Authors
Professor Alyn Morice A.H.Morice@hull.ac.uk
Foundation Chair and Professor of Respiratory Medicine
Jaclyn A. Smith
Lorcan McGarvey
Surinder S. Birring
Sean M. Parker
Alice Turner
Thomas Hummel
Isabella Gashaw
Lueder Fels
Stefan Klein
Klaus Francke
Christian Friedrich
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.
Citation
Morice, A., Smith, J. A., McGarvey, L., Birring, S. S., Parker, S. M., Turner, A., Hummel, T., Gashaw, I., Fels, L., Klein, S., Francke, K., & Friedrich, C. (2021). Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: A randomised, placebo-controlled, crossover phase 2a study. European respiratory journal, 58(5), Article 2004240. https://doi.org/10.1183/13993003.04240-2020
