Gefapixant, a P2X3 receptor antagonist, improved chronic cough severity and QOL, but 13% of patients discontinued due to taste-related side effects.
In an analysis of two datasets of patients with chronic cough (CC) of different duration but otherwise similar baseline characteristics, the P2X3 receptor antagonist gefapixant reduced cough severity and improved cough-related QOL. However, about 13% of patients discontinued the drug due to taste-related adverse events. These findings were presented at the 2023 ERS International Congress.
There are currently no licensed treatments for treatment of CC. However, P2X3 receptor antagonists seem to have a promising potential. The P2X3-receptor antagonist gefapixant significantly reduced objective cough frequency relative to placebo and improved patient-reported cough-specific QOL and cough severity in two pivotal phase 3 trials (COUGH-1 and COUGH-2) including patients with longstanding cough.
Moreover, in a phase 3b trial of patients with recent-onset CC, gefapixant improved cough-specific QOL and cough severity compared with placebo over 12 weeks. Participants in the phase 3 trials had a mean CC duration of about 11 years, whereas in the other trial, participants had a maximum cough duration of 8 weeks. As Imran Satia, MD, PhD, pointed out, the team wanted to find out whether the duration of CC affects the efficacy and safety profiles of twice-daily gefapixant (45 mg).
Other than cough duration, demographics and baseline characteristics were similar across datasets; most participants were female (>64%) and White (>72%). Patients from both datasets were from North America, Europe, Asia-Pacific, and Latin America populations. The treatment effect of gefapixant was evaluated in the Leicester Cough Questionnaire (LCQ). In this questionnaire, higher scores indicate better cough-specific QOL.
Baseline LCQ scores were comparable in both datasets (10.4 in the CC patients from the COUGH-1 and COUGH-2 trials and 10.8 in the patients from the phase 3a trial). Therapy with gefapixant led to an in increase in LCQ of 3.46 in the first dataset and 4.34 in patients with CC for less than 1 year. In addition, cough severity in a visual analogue scale (0-100 mm) improved similarly in both groups; it was reduced by –26.33 in the phase 3 trial group compared with –31.79 in the phase 3a group.
“We did not see any serious adverse event, but as most of you probably know, the most common side effects of gefapixant are any taste-related adverse event, 64% of these were dysgeusia. 13% of patients discontinued due to taste-related adverse events,” Dr. Satia explained. Results of this analysis suggest a similar favorable response to gefapixant 45 mg bid regardless of CC duration.
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