Gefapixant shows long-term efficacy for treatment of chronic cough

A pooled analysis of the COUGH-1 and COUGH-2 trials demonstrated long-term efficacy of twice-daily gefapixant out to 52 weeks in patients with refractory or unexplained chronic cough, according to data presented at the CHEST Annual Meeting.

“Refractory chronic cough ... and unexplained chronic cough ... are underappreciated conditions with unmet clinical needs, as there are no licensed or approved medications for these indications,” Peter Dicpinigaitis, MD, FCCP, professor of medicine and director of Montefiore Cough Center at the Albert Einstein College of Medicine at Montefiore Medical Center, Bronx, New York, said during a presentation.

COUGH-1 and COUGH-2 are global phase 3 randomized controlled trials that evaluated gefapixant (Merck), a P2X3 antagonist in adults with refractory and unexplained chronic cough. Previous results demonstrated that gefapixant 45 mg twice daily significantly reduced 24-hour cough frequency.

Long-term efficacy

At the CHEST Annual Meeting, Dicpinigaitis presented results of a pooled analysis of the two trials over 52 weeks of treatment with gefapixant.

The mean age of the patients in the trials was 58 years, 75% were women, all had chronic cough for at least 1 year and a baseline cough severity visual analogue scale (VAS) score of 40 mm or higher. Sixty-two percent of patients had refractory chronic cough and 38% had unexplained chronic cough. Patients were randomly assigned to twice-daily gefapixant 15 mg or 45 mg or to placebo.

Patient-reported outcomes assessed included the Leicester Cough Questionnaire, the Cough Severity VAS and Cough Severity Diary.

Patient-reported outcomes were improved by 4 weeks, with continued improvement over 52 weeks among those who received gefapixant 45 mg and placebo. Compared with placebo, patients assigned gefapixant 45 mg had improved response odds at 52 weeks in:

• Leicester Cough Questionnaire: OR = 1.72 (95% CI, 1.31-2.27);
• Cough Severity VAS: OR = 1.47 (95% CI, 1.15-1.89);
• Cough Severity Diary ( 1.3-point reduction): OR = 1.62 (95% CI, 1.23-2.15); and
• Cough Severity Diary ( 2.7-point reduction): OR = 1.57 (95% CI, 1.21-2.03).

Taste-related adverse events were the most common events in patients assigned gefapixant 45 mg. Few serious adverse events were reported in the gefapixant 45 mg (5.6%), gefapixant 15 mg (6%) and placebo (5.8%) groups.

“These results provide meaningful patient-relevant evidence in support of the long-term efficacy of gefapixant 45 mg twice daily for the treatment of patients with chronic cough,” Dicpinigaitis said.

Sustained treatment response

Dicpinigaitis also presented results of an exploratory, observational study in a subset of patients in the COUGH-1 and COUGH-2 trials that evaluated 3-month off-treatment durability of gefapixant in those with a treatment response after 52 weeks of treatment.

This study included 163 participants (mean age, 58.9 years; 70% women) with refractory or unexplained chronic cough. All participants completed 52 weeks of treatment, had 90% or greater adherent to their treatment, were at least 80% compliant with reporting patient-reported outcomes, and completed all baseline patient-reported outcome diaries and the week-52 Leicester Cough Questionnaire.

Participants were randomly assigned to continuous dosing with gefapixant 45 mg, gefapixant 15 mg or placebo twice daily. The off-treatment durability study began immediately after the extension period and continued for 12 weeks. During this time, researchers measured the Cough Severity Diary, Leicester Cough Questionnaire and Cough Severity VAS.

Gefapixant treatment durability was assessed as the proportion of participants with a treatment response at 52 weeks who also had a response at week 64 after 3 months off treatment.

Eighty-six percent of patients in the gefapixant 45 mg group who achieved a Cough Severity VAS response at 52 weeks also had a Cough Severity VAS response at 64 weeks, Dicpinigaitis said. Ninety-two percent of patients in the gefapixant 45 mg group who achieved a Cough Severity Diary response of at least a 1.3-point reduction at 52 weeks also had a response when assessed at 64 weeks. Seventy-one percent of patients in the gefapixant 45 mg group who achieved a Cough Severity Diary response of at least a 2.7-point reduction at 52 weeks also had a response when assessed at 64 weeks. Eighty percent of patients who received gefapixant 45 mg and achieved a Leicester Cough Questionnaire response at 52 weeks also had a response when assessed at 64 weeks.

“Although data from the small exploratory study are suggestive of sustained treatment response, further research is needed to better understand maintenance for treatment effect after this continuation,” Dicpinigaitis said.

References:

• Dicpinigaitis P, et al. Chest. 2021;doi:10.1016/j.chest.2021.07.2043.
• Dicpinigaitis P, et al. Chest. 2021;doi:10.1016/j.chest.2021.07.2044.