Additional Data on Possible Chronic Cough Therapy Presented at CHEST 2021

At the CHEST Annual Meeting 2021, attendees heard a readout from a durability study as well as pooled analyses from 2 phase 3 trials for gefapixant; both studies were presented by the lead investigator, Peter Dicpinigaitis, MD, professor of medicine at the Albert Einstein College of Medicine, director of the Montefiore Cough Center, and editor-in-chief of LUNG.

Gefapixant, a p2x3 receptor antagonist, is being reviewed by the FDA for treatment of refractory chronic cough (RCC) or unexplained chronic cough (UCC), with a decision expected by March 2022 (the first date was December 2021).*

RCC is cough that continues and is refractory to treatment of comorbid conditions associated with cough, whereas UCC is not associated with any comorbid conditions.

Previous results of COUGH-1 and COUGH-2, which were randomized, 52-week, double-blind, parallel-group, placebo-controlled phase 3 trials, showed that twice-daily treatment with gefapixant 45 mg significantly reduced patient-reported cough severity and improved cough-related quality of life.

In a presentation Tuesday, Dicpinigaitis shared results of an observational, exploratory trial looking at the durability of gefapixant in participants who had completed a year of treatment and then went off therapy for 3 months.¹ Eligible participants were those were 80% or more compliant with the completion of patient-reported outcome (PRO) entries and 80% or more adherent.

Responders at 52 weeks from baseline were defined as those who achieved at least a 30-mm reduction on the cough severity visual analog scale (VAS), at least a 1.3-point increase on the Leicester Cough Questionnaire (LCQ), or a reduction on the Cough Severity Diary (CSD); the CSD responders were grouped into those with reductions of at least 1.3 points and at least 2.7 points.

Treatment durability was defined as the proportion of responders in each treatment group (ie, placebo, gefapixant 15 mg BID, or gefapixant 45 mg BID) after the 3-month off-treatment phase by week 64.

Of 163 participants in the study, most were female and White; 55% had an RCC diagnosis and 45% had a UCC diagnosis. Participants who did not have PRO data available for week 64 were not included in the final analysis.

Using the VAS:

• In the 45-mg group, 74% of respondents showed improvement by week 52, and that climbed to 86% by week 64.
• In the 15-mg group, 43% responded, climbing to 67% by week 64.
• In the placebo group, 52% responded by week 52, climbing to 91% by week 64.

Using the LCQ, 81% of those in the 45-mg group were responders at week 52, dipping slightly to 80% at week 64; 83% of those in the 15-mg group achieved a response at week 52, rising to 87% at week 63; and finally, in the placebo group, 63% had a response at week 52, rising to 88% after 3 months.

Using the CSD, the proportion of those in the 45-mg group who achieved at least a 2.7-point reduction were 79% at week 52, dipping to 71% at week 64; in the 15-mg group, 43% responded at week 52, rising to 80% at week 64; and in the placebo group, 44% responded at week 52, rising to 90% at week 64.

Dicipinigaitis noted that this was an observational pilot study with a small number of participants and that additional research is needed to better understand the durability of treatment effect after active drug treatment ends. Missing data assumptions may over- or underestimate responder rates, he said.

In the pooled analyses of the phase 3 trials involving 2044 participants, gefapixant 45 mg showed efficacy over 52 weeks of treatment as assessed by the LCQ, the VAS, and the CSD. ² Scores for all of the PROs improved for both gefapixant and placebo, although the improvement was greater for the gefapixant group.

Discontinuations due to taste-related adverse events were dose related, and the occurrence of serious adverse events was similar in both groups.

"These results provide meaningful patient-relevant evidence in support of the long-term efficacy of gefapixant 45 mg BID for the treatment of patients with chronic cough," he concluded.

References

1. Dicpinigaitis P, Birring S, McGarvey L, et al. Preliminary estimates of off-treatment durability of gefapixant across two phase 3 studies of participants with refractory or unexplained chronic cough. Presented at: CHEST Annual Meeting 2021; October 17-20, 2021. Abstract 2361A.

2. Dicpinigaitis Birring S, Morice A, et al. Treatment of refractory or unexplained chronic cough with gefapixant, a p2x3 receptor antagonist, over 52 weeks in two phase III clinical trials. Presented at: CHEST Annual Meeting 2021; October 17-20, 2021. Abstract 2363A.

*This story was updated with the correct PDUFA date.