Lyfnua (gefapixant) / Merck (MSD) - LARVOL DELTA

Association between baseline cough burden and gefapixant discontinuations due to taste-related adverse events (BTS WM 2025) - P3 | "bFor the LCQ, a lower total score indicates a higher cough burden Conclusions These findings suggest that patients with higher baseline cough burden may be more willing to continue treatment regardless of taste AEs. Because results of this post hoc analysis are observational, they require further confirmation."

Adverse events • Chronic Cough • Cough • Respiratory Diseases

Clinically relevant attenuation of cough with gefapixant: a post hoc analysis (BTS WM 2025) - P3 | "Download figure Open in new tab Download powerpoint Abstract P116 Figure 1 Percentage of participants by PGIS categories for (A) LCQ and (B) cough severity VAS scores at baseline and over time of treatment with gefapixant 45 mg twice daily vs placebo. LCQ, Leicester Cough Questionnaire; PGIS, Patient Global Impression of Severity; VAS, visual analog scale Conclusions A sizeable and higher percentage of participants treated with gefapixant vs placebo experienced clinically relevant attenuation of cough, which increased over time."

Clinical • Retrospective data • Chronic Cough • Cough • Respiratory Diseases

Patient global impression of change: contextualizing patient-reported outcomes in gefapixant phase 3 trials (BTS WM 2025) - P3 | "BID, twice daily; CSD, Cough Severity Diary; LCQ, Leicester Cough Questionnaire; PGIC, Patient Global Impression of Change; PRO, patient-reported outcome; VAS, visual analog scale Conclusions In COUGH-1/-2, there were more PGIC responders in the gefapixant vs placebo group. The relationship between responses on the PGIC and cough PROs suggests cough PRO responses reported in COUGH-1/-2 are similar to the observed results of the PGIC, an endpoint that may be more easily interpreted in clinical practice."

Clinical • P3 data • Patient reported outcomes • Cough • Respiratory Diseases

Comparative Analysis of Classic and Novel Antitussives on Cough Suppression in Guinea Pigs. (PubMed, Pharmaceutics) - " This study evaluated and compared the antitussive efficacy of classic (codeine, cloperastine, dextromethorphan, levodropropizine) and novel (gefapixant) agents using a citric acid-induced cough model in guinea pigs. These findings highlight the potential clinical relevance of both centrally and peripherally acting non-opioid alternatives. Continued investigation of these agents may help address the unmet need for safer and more effective cough treatments."

Journal • Cough • Respiratory Diseases

Vitamin B6 (pyridoxal 5' phosphate) antagonizes carotid body P2X3 receptors in hypertension. (PubMed, Cardiovasc Res) - "Our findings suggest that PLP binds to and antagonizes P2X3R and is a viable candidate for larger clinical trials to treat CB dysregulation in cardiovascular diseases."

Clinical • Journal • Cardiovascular • Hypertension

Gefapixant Citrate, a Selective P2X3 Receptor Antagonist, May Improve Cancer-Related Hypergeusia: A Case Report. (PubMed, J Palliat Med) - "Gefapixant citrate may improve hypergeusia and sustain oral intake in patients with refractory cough, suggesting its potential use in the management of hypergeusia. However, caution is required owing to its limited efficacy in treating cancer cachexia and possible taste-related adverse effects."

Journal • Anorexia • Cachexia • Cough • Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor

Gefapixant for the treatment of Refractory or Unexplained Chronic Cough (RCC) (ERS 2025) - "Sponsored by Merck (MSD)"

Chronic Cough • Cough • Renal Cell Carcinoma • Respiratory Diseases

Impact of Gefapixant on Chronic Cough in a Real-World Setting (ERS 2025) - "The baseline severity of patients in our cohort was higher than in pivotal trials. A significant improvement was seen in half of the patients. Dysgeusia was the most common side effect."

Clinical • Real-world • Real-world evidence • Allergic Rhinitis • Asthma • Chronic Cough • CNS Disorders • Cough • Depression • Gastroenterology • Gastroesophageal Reflux Disease • Immunology • Inflammation • Psychiatry • Respiratory Diseases

Patient Global Impression of Change: contextualizing patient-reported outcomes in gefapixant phase 3 trials (ERS 2025) - P3 | "In COUGH-1/-2, there were more PGIC responders in the gefapixant vs pbo group. The relationship between responses on the PGIC and cough PROs suggests cough PRO responses reported in COUGH-1/-2 are similar to the observed results of the PGIC, an endpoint that may be more easily interpreted in clinical practice."

Clinical • P3 data • Patient reported outcomes • Cough • Respiratory Diseases

Time course of patient-reported outcomes among gefapixant responders vs nonresponders: post hoc analysis (ERS 2025) - P3 | "Compared with self-reported PGIC responders, nonresponders exhibited poorer cough PROs over time. Their improvements were noticeable by Wk 4 but remained markedly lower than levels achieved by responders; even by Wk 52 of treatment, nonresponders did not reach outcomes attained by responders at Wk 4."

Clinical • Patient reported outcomes • Retrospective data • Cough • Respiratory Diseases

Clinically relevant attenuation of cough with gefapixant: a post hoc analysis (ERS 2025) - P3 | "A sizeable and higher percentage of participants treated with gefapixant vs pbo experienced clinically relevant attenuation of cough, which increased over time."

Clinical • Retrospective data • Chronic Cough • Cough • Respiratory Diseases

Association between baseline cough burden and gefapixant discontinuations due to taste-related adverse events (ERS 2025) - P3 | "These findings suggest that patients with higher baseline cough burden may be more willing to continue treatment regardless of taste AEs. Because results of this post hoc analysis are observational, they require further confirmation."

Adverse events • Chronic Cough • Cough • Respiratory Diseases

Efficacy and tolerability of gefapixant in chronic cough: a single-center retrospective study (ERS 2025) - "Gefapixant rapidly improved subjective cough symptoms in a real-world setting; however, the high incidence of taste disturbances adversely affected adherence. Although effective for short-term management, strategies to mitigate taste-related side effects are needed for optimizing long-term treatment."

Retrospective data • Chronic Cough • Cough • Respiratory Diseases

Gefapixant for Refractory Cough in Interstitial Lung Disease (ERS 2025) - "Conclusion In this study, we also evaluated the difference between subjective and objective evaluations of cough and the relationship between efficacy and side effects. These findings also highlight the complexity of treating this condition and underscore the need for further investigation into the mechanisms of gefapixant and its role within the broader therapeutic landscape of ILD."

Chronic Cough • Cough • Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Real-world usage and response to gefapixant in refractory chronic cough. (PubMed, ERJ Open Res) - "Taste disturbance was not associated with response to gefapixant and was less frequent in patients with cough triggers such as smoke, dry air, or scents, than in those without these triggers. Gefapixant demonstrated a rapid and effective antitussive effect in this multicentre, real-world study."

Journal • Real-world evidence • Asthma • Chronic Cough • Cough • Immunology • Pulmonary Disease • Respiratory Diseases

Disease finds its identity with treatment in the real world: the use of gefapixant in chronic cough. (PubMed, ERJ Open Res) - "Gefapixant offers promising targeted therapy, and real-world evidence highlights its potential in improving outcomes and advancing our disease understanding. https://bit.ly/42U2p6j."

Journal • Real-world evidence • Chronic Cough • Cognitive Disorders • Cough • Pulmonary Disease • Respiratory Diseases

Sun Pharma Gets SEC Nod To Begin Phase III Trial Of Cough Drug Gefapixant (Medical Dialogues) - "The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has recommended granting permission to initiate a Phase III clinical trial for the new drug Gefapixant Tablets 45 mg, based on the bioequivalence (BE) study submitted by Sun Pharma Laboratories. This recommendation was made following a detailed review of the BE study report presented during the SEC Pulmonary meeting held on 28th May 2025...Following deliberation, the SEC concluded that the results of the BE study supported further clinical development and therefore recommended the initiation of the Phase III clinical trial. The committee has directed the company to submit the results of the Phase III trial to CDSCO for further evaluation."

New P3 trial • Regulatory • Chronic Cough

Exploring the Potential of a P2X3 Receptor Antagonist: Gefapixant in the Management of Persistent Cough Associated with Interstitial Lung Disease. (PubMed, Medicina (Kaunas)) - " Gefapixant appears to be effective in reducing refractory cough related to ILD, although these results were not statistically significant because its effectivity widely varied across individuals. Further investigation is needed to identify patient subgroups with the greatest potential for treatment responsiveness."

Journal • Chronic Cough • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatology

Safety, Tolerability, and Pharmacokinetics of Filapixant, a Highly Selective P2X3 Receptor Antagonist, in an Ascending-Single-Dose First-in-Human Study. (PubMed, Pharmaceuticals (Basel)) - P1 | "It was anticipated that filapixant would cause fewer taste-related side effects compared to the unselective P2X3/P2X2/3 antagonist gefapixant and the less selective P2X3 antagonist eliapixant. The number of taste side effects was unexpectedly high considering the high in vitro P2X3 receptor selectivity. Factors other than selectivity are needed to explain taste profile differences between P2X3 antagonists."

Clinical • Journal • P1 data • PK/PD data • Pain

In Vitro Characterization of CHF6795, A New Potent and Selective P2X3 Inhibitor With Anti-tussive Properties (ATS 2025) - "Indeed, a first P2X2/3 inhibitor, gefapixant, has reached the market for the treatment of CC. CHF6795 is a new, highly effective, and selective P2X3 inhibitor being explored as an anti-tussive agent. It shows great promise due to its specific targeting, which should avoid any impact on taste perception."

Preclinical • Chronic Cough • Cough • Respiratory Diseases

Investigating Camlipixant P2X3 Selectivity and Taste Disturbance: A Model-Based Dose-Response Meta-Analysis (ATS 2025) - P3 | "Other P2X3 antagonists of different magnitudes of selectivity have been investigated for RCC: sivopixant (262×), eliapixant (13×), gefapixant (1.5×), and filapixant (unknown). In this model-based dose-response meta-analysis, the highly selective P2X3 antagonist camlipixant demonstrated placebo-like rates of dysgeusia over the clinical dose range modelled. After adjusting for relative selectivity, all P2X3 antagonists fell on the same tolerability dose-response curve, and the dosage of camlipixant currently under investigation in the CALM-1 and CALM-2 Phase 3 clinical trials (50 mg BID; NCT05599191, NCT05600777) was predicted to result in substantially lower rates of dysgeusia compared with a similar dosage of gefapixant."

Retrospective data • Chronic Cough • Cough • Renal Cell Carcinoma • Respiratory Diseases

CHF6795 a Novel, Potent, and Selective Oral P2X3R Antagonist Showing Strong Anti-tussive Effect and No Taste Alteration in Preclinical Models (ATS 2025) - "Indeed, a first P2X2/3R antagonist, gefapixant, has reached the market for the treatment of CC. CHF6795 was selected as a drug candidate for the treatment of CC due to P2X3R selectivity, potency and efficacy in inducing an anticough effect without taste alteration at the effective doses. CHF6795 currently completed Ph1 study."

Preclinical • Chronic Cough • Cough • Respiratory Diseases

The P2X3 receptor blocker AF-353 (Ro-4) reduces bioenergetic index of a primary mixed culture of hippocampal neurons. (PubMed, Biomed Khim) - "These include 5-(5-iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine (Ro-4 or AF-353), gefapixant, which have a good pharmacokinetic profile and are less active with respect to a wide range of kinases, receptors, and ion channels...The neuronal BHI decrease in the postnatal culture was 68% compared to the control. The obtained results indicate the effect of AF-353 on mitochondrial respiration of a primary mixed culture of hippocampal neurons; this reveals the potential of the P2X3 receptor as a pharmacological target in hypoxic conditions of the brain."

Journal • Mood Disorders • Pain • Psychiatry

RESTORE: The Real-world Treatment Satisfaction by Gefapixiant in RCC (clinicaltrials.gov) - P=N/A | N=63 | Recruiting | Sponsor: Nagoya City University | Not yet recruiting ➔ Recruiting

Enrollment open • HEOR • Real-world evidence • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

What role for ▼gefapixant in chronic cough? (PubMed, Drug Ther Bull) - No abstract available

Journal • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases