Gefapixant curbs chronic cough independent of its duration

An analysis of 2 datasets of patients with chronic cough (CC) of different disease duration showed that gefapixant reduced cough severity and improved cough-related quality-of-life, independent of cough duration. Unfortunately, taste-related adverse events during gefapixant use were common and led to a discontinuation rate of about 13%.
The P2X3-receptor antagonist gefapixant has shown potential to treat CC, a condition currently lacking an approved treatment option. The agent significantly reduced objective cough frequency relative to placebo and improved patient-reported, cough-specific quality-of-life and cough severity in 2 pivotal phase 3 trials (COUGH-1 [NCT03449134] and COUGH-2 [NCT03449147]) including patients with longstanding cough [1]. Moreover, in a phase 3b trial (NCT04193202) of patients with recent-onset CC, gefapixant improved cough-specific quality-of-life and cough severity compared with placebo over 12 weeks [2]. Participants in the COUGH 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 Prof. Imran Satia (McMaster University, Canada) pointed out, with their current study, the researchers determined if the duration of CC affects the efficacy and safety profiles of twice-daily gefapixant (45 mg) [3]. Other than cough duration, demographics and baseline characteristics were similar across data sets: most participants were women (>64%) and white (>72%); both patient groups spanned North America, Europe, Asia-Pacific, and Latin America. Treatment effect of gefapixant was evaluated in the Leicester Cough Questionnaire (LCQ). In this questionnaire, higher scores indicate better cough-specific quality-of-life. Baseline LCQ scores were comparable in both patient groups (10.4 in the CC patients from the COUGH-1 and COUGH-2 trials and 10.8 in the patients from the recent-onset CC trial).

Therapy with gefapixant led to an in increase in LCQ of 3.46 in the COUGH participants and 4.34 in the patients suffering from CC <1 year (see Figure). 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 COUGH trial group compared with -31.79 in the recent-onset CC group.
“We did not see any serious adverse events, but as expected, the most common side effects of gefapixant were taste-related; 64% of these were dysgeusia. Overall, 13% of patients discontinued due to taste-related adverse events,” Prof. Satia explained.
Results of this analysis suggest a similar favourable response to gefapixant 45 mg twice daily, regardless of CC duration.

Figure: Total score changes in the Leicester Cough Questionnaire from baseline at week 12 [3]

1. McGarvey LP, et al. Lancet 2022;399:909-23.
2. McGarvey LP, et al. Lung 2023;20:111-118.
3. Satia I, et al. Gefapixant efficacy and safety in participants with history of refractory or unexplained chronic cough for ≥ 1 vs < 1 year. Abstract 3290, ERS International Congress 2023, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023