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

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

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

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

Therapeutic and Mechanistic Advances in Chronic Cough. (PubMed, Ann Allergy Asthma Immunol) - "Additionally, a new peripherally acting oral P2×3 receptor antagonist, gefapixant, has been approved in the EU, UK, Switzerland, and Japan, though not in the USA or Canada. Emerging treatments hold promise for improving management in the future."

Journal • Review • Asthma • Chronic Cough • Cough • Gastroenterology • Gastroesophageal Reflux Disease • Pulmonary Disease • Respiratory Diseases

Responder analysis of Leicester cough questionnaire domains from phase 3 trials of gefapixant (COUGH-1/COUGH-2) (BTS WM 2024) - P3 | "The gefapixant group also experienced greater odds of achieving clinically meaningful responses across domains ( figure 1B ). Conclusions Participants who received gefapixant were more likely to report clinically meaningful improvements in LCQ social, psychological, and physical domains compared with participants who received placebo, supporting the overall benefit of gefapixant on cough-specific quality of life."

P3 data • Chronic Cough • Cough • Respiratory Diseases

The Clinical Approach to Chronic Cough. (PubMed, J Allergy Clin Immunol Pract) - "First-line treatments now include neuromodulators and speech therapy with one P2X3 receptor antagonist (gefapixant) recently licensed in the EU, UK and Japan. Despite these advances, patient responses remain variable, underscoring the ongoing need for research into the pathophysiology and treatment of RCC. This article reviews current investigations and management options in treating chronic cough and RCC."

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

A Study to Evaluate the Efficacy and Safety of Gefapixant (MK-7264) in Women With Endometriosis-Related Pain (MK-7264-034) (clinicaltrials.gov) - P2 | N=187 | Completed | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2a ➔ P2

Phase classification • Endometriosis • Gynecology • Pain • Women's Health

Efficacy and Safety of Gefapixant (MK-7264) in Women With Chronic Cough and Stress Urinary Incontinence (MK-7264-042) (clinicaltrials.gov) - P3 | N=376 | Completed | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P3b ➔ P3

Phase classification • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases • Urinary Incontinence • Urology

P2X3 and P2X2/3 Receptors Inhibition Produces a Consistent Analgesic Efficacy: A Systematic Review and Meta-Analysis of Preclinical Studies. (PubMed, Eur J Pharmacol) - "P2X3 and P2X2/3 receptor inhibitors showed a good analgesic efficacy in preclinical studies, which was dependent on the pain etiology, pain outcome measured, the drug used and its route of administration. Further research is needed to assess the clinical utility of these preclinical findings."

Journal • Preclinical • Retrospective data • Review • Endometriosis • Gynecology • Immunology • Neuralgia • Oncology • Osteoarthritis • Pain • Rheumatology • Women's Health

Pharmacological differences in postoperative cutaneous sensitivity, pain at rest, and movement-induced pain in laparotomized mice. (PubMed, Biomed Pharmacother) - "The standard analgesics morphine and ibuprofen induced distinct patterns of outcome-dependent effects...We tested the effects of gefapixant, an antitussive drug targeting non-peptidergic nociceptors through P2X3 antagonism, and olcegepant, an antimigraine drug acting as a CGRP antagonist...In conclusion, tactile allodynia, pain at rest, and movement-induced pain after surgery have different pharmacological profiles, and none of the three aspects of postoperative pain can predict the effects of a given intervention on the other two. Combining these measures provides a more realistic view of postoperative pain and has the potential to benefit analgesic development."

Journal • Preclinical • CNS Disorders • Migraine • Pain

Refractory or unexplained chronic cough: Treatment with gefapixant (ERS 2024) - "Sponsored by Merck (MSD) ."

Chronic Cough • Cough • Respiratory Diseases

453: Gefapixant for the treatment of patients with refractory or unexplained chronic cough (RCC) (ERS 2024) - "Sponsored by Merck (MSD) ."

Clinical • Chronic Cough • Cough • Renal Cell Carcinoma • Respiratory Diseases

Response to Gefapixant in the Cough Clinic: A Real-world Study (ERS 2024) - "Patients appear to respond rapidly in multiple aspects of cough. An ERS NeuroCOUGH CRC site"

Clinical • Real-world • Real-world evidence • Chronic Cough • Cough • Respiratory Diseases

Responder analysis of Leicester Cough Questionnaire domains from phase 3 trials of gefapixant (COUGH-1/COUGH-2) (ERS 2024) - P3 | "A higher percentage of pts receiving gefapixant reported clinically meaningful improvements in LCQ social, psychological, and physical domains vs pbo, supporting the broad benefit of gefapixant on cough-specific quality of life."

P3 data • Chronic Cough • Cough • Respiratory Diseases

Randomized, controlled, proof-of-concept trial of gefapixant for endometriosis-related pain. (PubMed, Fertil Steril) - P2a | "Gefapixant 45mg twice-daily was not shown to be superior to placebo in reducing endometriosis-related pain, although the results directionally favored gefapixant. This trial result should be considered inconclusive given possible issues with treatment compliance. (Clinical trial registration: NCT03654326)."

Clinical • Journal • Endometriosis • Gynecology • Musculoskeletal Pain • Pain • Women's Health

Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial. (PubMed, Lancet Respir Med) - P3b | "Gefapixant 45 mg twice daily is the first treatment to show efficacy versus placebo in reducing CSUI episodes in participants with refractory or unexplained chronic cough."

Journal • P3 data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases • Urinary Incontinence • Urology

The discovery and development of gefapixant as a novel antitussive therapy. (PubMed, Expert Opin Drug Discov) - "This research and personalized treatment approaches are key to optimizing gefapixant therapy, ensuring improved management of chronic cough while reducing adverse effects. However, pharmaceutical trials and proposals must be adapted to align with each regulatory body's specific requirements and concerns."

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

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

HEOR • New trial • Real-world • Real-world evidence • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Gefapixant as a P2X3 receptor antagonist treatment for obstructive sleep apnea: a randomized controlled trial. (PubMed, J Clin Sleep Med) - P1 | "Gefapixant, while generally well tolerated, did not reduce OSA severity in patients with chemoreflex-dependent OSA. P2X3 receptor antagonism is unlikely to provide an avenue for therapeutic intervention in OSA."

Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Physiologically Based Biopharmaceutics Modeling for Gefapixant IR Formulation Development and Defining the Bioequivalence Dissolution Safe Space. (PubMed, AAPS J) - " PBBM was also applied to evaluate gastric pH-mediated drug-drug-interaction potential with co-administration of a proton pump inhibitor (PPI), omeprazole. An extended virtual dissolution bioequivalence safe space was established.  Gefapixant drug product batches are anticipated to be bioequivalent with the clinical reference batch when their dissolution is > 80% in 60 minutes. PBBM established a wide dissolution bioequivalence space as part of assuring product quality."

Journal

Benefit-risk profile of P2X3 receptor antagonists for treatment of chronic cough: Dose-response model-based network meta-analysis. (PubMed, Chest) - "When used at safe doses, gefapixant had a favorable risk-benefit profile compared to the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway."

Benefit-risk assessment • Journal • Retrospective data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Real World Experience of Gefapixant Prescribing (ATS 2024) - "Although numbers are small, change in PROs are consistent with that seen in RCTs. Patients appear to respond rapidly and provide positive qualitative feedback."

Clinical • Real-world • Real-world evidence • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases