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

A granular analysis of cough counting (ERS 2026) - "Mean cough density was reduced by 8 coughs/hour on gefapixant versus 0 cough/hour on placebo. Cough relief and cough density provide a more granular picture of observed cough events which may be more readily communicated to those unfamiliar with cough counting."

Chronic Cough • Cough • Respiratory Diseases

Quality-of-Life Outcomes in Chronic Cough Patients Treated With Gefapixant: Real-World Evidence From a Retrospective Cohort Study (ERS 2026) - "Conclusion Gefapixant appears beneficial for unexplained or refractory chronic cough, with most patients showing improved quality of life on LCQ. Dysgeusia remains a common limiting side effect, warranting further research to improve tolerability."

HEOR • Real-world • Real-world evidence • Retrospective data • Chronic Cough • Cough • Immunology • Respiratory Diseases

Clinical Experience with Gefapixant in a Specialized Chronic Cough Clinic: Navigating the P2X3 Pathway (ERS 2026) - "Candidates for gefapixant present long-standing disease and significant treatment fatigue. High cost remains the main barrier to access, while dysgeusia and perceived lack of efficacy are the primary drivers of discontinuation."

Clinical • Chronic Cough • Cough • Gastroesophageal Reflux Disease • Renal Cell Carcinoma • Respiratory Diseases

Pilot study: antitussive effect of gefapixant in dogs with chronic cough. (PubMed, J Vet Med Sci) - "No serious adverse event was definitively attributed to gefapixant, although one dog with megaesophagus developed pneumonia. These preliminary observations warrant further controlled studies incorporating objective cough monitoring to determine the efficacy and safety of gefapixant in dogs."

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

Chronic Cough (PubMed, Dtsch Med Wochenschr) - "Thus, it may be difficult to prove the therapeutic effect of a new drug, i.e. Gefapixant, the first recently approved treatment for RCC/UCC. We discuss the different CC phenotypes and endotypes, they will require development of new differentiated therapies. Finally, we discuss some new pipeline drugs in development."

Journal • Review • Chronic Cough • Cough • Immunology • Pulmonary Disease • Renal Cell Carcinoma • Respiratory Diseases

Selective P2X3 versus dual P2X2/3 receptor antagonists in refractory chronic cough: a systematic review and dose-response meta-analysis of randomized controlled trials. (PubMed, Purinergic Signal) - "While dual antagonists (gefapixant) demonstrate robust antitussive efficacy, their clinical use is limited by taste disturbance resulting from P2X2/3 inhibition in gustatory pathways...Among selective agents, camlipixant (≥ 50 mg BID) achieved clinically meaningful cough reduction (- 34%) with minimal dysgeusia (5-7%). These findings demonstrate a mechanistically defined benefit-risk trade-off in purinergic receptor targeting, supporting selective P2X3 antagonism as a more favourable strategy for modulating ATP-driven airway sensory signalling in RCC while preserving tolerability."

Clinical • Journal • Retrospective data • Review • Chronic Cough • Cough • Pulmonary Disease • Renal Cell Carcinoma • Respiratory Diseases

Effectiveness of the P2X3 Antagonist Gefapixant for Refractory Atopic Cough: A Retrospective Cohort Study. (PubMed, J Asthma Allergy) - "The P2X3 antagonist gefapixant appeared to improve patient-reported symptoms and cough reflex hypersensitivity in a retrospective cohort of patients with refractory atopic cough. These findings suggest P2X3 antagonists may be a treatment option for refractory atopic cough, possibly through possibly through reducing hypersensitivity of airway C fibers."

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

Targeting P2X receptor signaling for chronic visceral pain and beyond. (PubMed, Neuropharmacology) - "The first-generation P2X3/P2X7 antagonists (e.g., AF-219, AZD-9056, NC-2600) failed in clinical trials, primarily due to species-specific receptor pharmacology, the lack of ATP-based biomarkers for patient stratification, and irreversible central sensitization driven by epigenetic marks. To overcome these hurdles, we propose a precision-medicine framework that includes: (1) CRISPR-dCas9-based epigenome editing as a potential one-time "pain-memory eraser"; (2) patient stratification using sweat-ATP levels; and (3) human iPSC-derived neuron screening to improve translational predictability. This integrated approach holds promise not only for CVP related to irritable bowel syndrome (IBS), but also for other pain conditions."

Journal • Review • Gastrointestinal Disorder • Pain

Pharmacology of Cough. (PubMed, Otolaryngol Clin North Am) - "Neuromodulators such as gabapentin, pregabalin, and tramadol have been repurposed to treat this hypersensitivity similar to other neuropathic pain conditions. A new class of drugs, P2X3 antagonists, have emerged as another possibility for treating individuals with chronic cough; however, Food and Drug Administration approval is still pending."

Journal • Review • Chronic Cough • Cough • Immunology • Infectious Disease • Neuralgia • Pain • Pulmonary Disease • Respiratory Diseases

Structure of the human P2X3 receptor reveals the basis for subtype-selective inhibition by sivopixant. (PubMed, PLoS Biol) - "Gefapixant, a negative allosteric modulator (NAM) of P2X3 receptors, has been approved in some countries for the treatment of chronic cough; however, its limited selectivity for P2X3 homomers over P2X2/P2X3 heteromers is associated with taste disturbance as a prominent adverse effect. Structural comparisons across P2X subtypes, together with patch-clamp analyses of gain-of-function mutants that confer sensitivity to two investigational drugs, sivopixant and camlipixant, provided a broadly applicable structural framework for subtype selectivity. Furthermore, structural comparisons with apo and ATP-bound open states of P2X3 receptors, together with molecular dynamics simulations, revealed that sivopixant expands the upper-body domain to suppress the lower-body movements required for channel activation, thereby preventing channel opening even in the presence of ATP."

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

Cryo-EM structures of human P2X2/3 heteromer channel reveal the structural basis of ligand selectivity. (PubMed, Sci Adv) - "Structural and functional analyses show that gefapixant binds a conserved interfacial allosteric pocket, explaining its poor selectivity and taste-related side effects, whereas the next-generation antagonist camlipixant exploits a divergent vestibular site unique to P2X3, conferring >10,000-fold selectivity and improved tolerability. These findings establish a structural framework for P2X2/3 assembly and drug recognition and provide a roadmap for rational design of selective P2X modulators with enhanced safety and efficacy."

Journal • Cough • Respiratory Diseases

Purinergic Receptors as Emerging Targets in the Management of Chronic Cough: From Pathophysiology to Clinical Application. (PubMed, J Investig Allergol Clin Immunol) - "This comprehensive review of the pathophysiology of chronic cough focuses on the role of purinergic signaling, with an examination of the preclinical and clinical evidence supporting the efficacy of P2X3 antagonists, such as gefapixant, in reducing cough frequency. Furthermore, we discuss the clinical and safety considerations of these novel drugs, including the main challenge of taste-related adverse effects, and explore future perspectives, such as the development of more selective molecules and the identification of biomarkers to guide personalized treatment strategies. The advent of purinergic receptor modulation marks a significant milestone in the management of chronic cough, offering new hope for patients with this refractory condition."

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

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