Gefapixant Associated With Significant Improvements in Chronic Cough

The P2X3 receptor antagonist gefapixant successfully improved quality-of-life (QOL) scores and cough severity in patients with refractory or unexplained chronic cough, according to results of 2 phase 3 trials presented at the European Respiratory Society International Congress 2021.

The posters reviewed results from 52 weeks of analysis in COUGH-1 and COUGH-2, which were randomized, double-blind, parallel-group, placebo-controlled trials. The first poster evaluated quality of life using the Leicester Cough Questionnaire (LCQ).¹

“Chronic cough is associated with a significant quality-of-life burden,” explained presenter Surinder S. Birring, MD, professor of respiratory medicine at King’s College Hospital and King’s College London.

The LCQ is a validated patient-reported outcome tool used to assess cough-specific QOL burden. It includes 3 subdomains—physical, psychological, and social—which are scored from 1 to 7 with a lower score indicating worse quality of life.

In the study, a LCQ total score change of ≥ 1.3 points from baseline was considered clinically meaningful.

A total of 2044 patients were recruited (730 in COUGH-1 and 1314 in COUGH-2). Patients were randomized to receive placebo, gefapixant 15 mg twice daily (BID), or gefapixant 45 mg BID. COUGH-1 was a 12-week trial and COUGH-2 was a 24-weeks trial, but both were extended to 52 weeks.

Across all 3 groups and both studies, 75% of participants were female, and the mean age was 58.4 years, which was similar across all groups. At baseline the mean LCQ scores were similar.

Improvements in the total LCQ score in the gefapixant groups vs placebo were seen as early as 4 weeks and maintained throughout the duration of the 52-week extension period. The subdomain scores were also higher for the gefapixant groups during the study and were maintained throughout the 52 weeks.

The odds of achieving LCQ score improvement of ≥ 1.3 points was significantly greater for the gefapixant 45 BID group compared with the placebo group, Birring said.

The second poster focused on patient-reported cough severity using the visual analogue scale (VAS) for the same trials.² The VAS is a 100 mm scale with 0 meaning no cough. Patients with a ≥ 30 mm reduction in the VAS were considered treatment responders.

Enrolled participants had a mean weekly cough severity VAS between 67 mm and 69 mm at baseline.

Since gefapixant 15 mg BID didn’t achieve a statistical significance from placebo in the primary end point of 24-hour cough frequency, only results from gefapixant 45 mg BID were reported.

Treatment with gefapixant led to a reduction in VAS scores during the main study that was maintained to the end of the 52-week extension period.

Patients on gefapixant were nearly 50% more likely to achieve a meaningful reduction in cough severity by week 24. The proportion of patients demonstrating a meaningful reduction in cough severity was:

• At 12 weeks (COUGH-1 only), 41% of patients on gefapixant vs 31% on placebo (estimated odds ratio [OR] 1.54; 95% CI, 1.03-2.30)
• At 24 weeks: in COUGH-1, 49% on gefapixant vs 34% on placebo (estimated OR 1.82; 95% CI, 1.21-2.73) and in COUGH-2 53% on gefapixant vs 41% on placebo (estimated OR 1.65; 95% CI, 1.23-2.22)
• At 52 weeks: in COUGH-1, 53% on gefapixant vs 42% on placebo (estimated OR 1.57; 95% CI, 1.02-2.41) and in COUGH-2, 62% on gefapixant vs 53% on placebo (estimated OR 1.45; 95% CI, 1.07-1.98)

“In the phase 3 trials of COUGH-1 and COUGH-2, treatment with gefapixant 45 mg taken twice daily was associated with significant improvements in objective cough frequency and cough-related quality of life,” said presenter Peter V. Dicpinigaitis, MD, professor of medicine at the Albert Einstein College of Medicine, director of the Montefiore Cough Center, and editor-in-chief of LUNG.

References

1. Birring SS, Smith JA, Morice A, et al. The Leicester Cough Questionnaire in two phase 3 trials of gefapixant in chronic cough. Presented at the European Respiratory Society International Congress 2021. Abstract 1587.

2. Dicpinigaitis PV, Birring SS, Morice A, et al. Patient-reported chronic cough severity over 52 weeks in two phase 3 trials of gefapixant. Presented at the European Respiratory Society International Congress 2021. Abstract 1588.