camlipixant (GSK5464714) / GSK - LARVOL DELTA

ATP-P2X3 Signaling as a Shared Neural Sensitization Pathway in Endometriosis and Irritable Bowel Syndrome: Mechanisms and Therapeutic Implications. (PubMed, Biomedicines) - "We summarize experimental and clinical evidence supporting P2X3 as a therapeutic target and discuss the development of selective P2X3 antagonists, including gefapixant, eliapixant, sivopixant, and camlipixant. Current evidence is predominantly preclinical, underscoring the need for biomarker-driven translational studies and clinical trials. Overall, ATP-P2X3 signaling represents a promising shared mechanistic pathway linking endometriosis and IBS and a potential target for the development of precision, nonopioid therapies for chronic pelvic and visceral pain."

Journal • Review • Chronic Cough • Cough • Endometriosis • Gastrointestinal Disorder • Gynecology • Immunology • Inflammation • Musculoskeletal Pain • Pain • Pulmonary Disease • Respiratory Diseases • Women's Health

A Study to Investigate the Difference In Blood Levels of Camlipixant Between Different Camlipixant Formulation Prototypes (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: GlaxoSmithKline | N=28 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Cough • Respiratory Diseases

Studies of transition metal-catalyzed asymmetric ketone reductions for GSK's new route to Camlipixant (ACS-Fall 2026) - "However, surprisingly high enantiomeric excesses (>90%) were observed using a chiral bisphosphine-ruthenium catalyst, which likely proceeds through an inner-sphere hydrogenation pathway. Studies on the substrate and catalyst features that lead to this high selectivity are ongoing in our group."

Safety, Tolerability, and Pharmacokinetics of Oral Camlipixant: A Randomized First-In-Human Study Using Single and Multiple Ascending Doses. (PubMed, J Clin Pharmacol) - "Pharmacokinetics were unaffected by food (geometric mean fed/fasted ratio Cmax 91.4% [90% confidence interval, CI, 69.8-119.6]; AUC0-∞ 105.5% [90% CI, 89.8-124.0]). In summary, camlipixant was well tolerated, with pharmacokinetics supporting BID dosing and further clinical development for refractory chronic cough."

Clinical • First-in-human • Journal • P1 data • PK/PD data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

A Study to Investigate the Difference In Blood Levels of Camlipixant Between Different Camlipixant Formulation Prototypes (clinicaltrials.gov) - P1 | N=28 | Suspended | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Suspended

Trial suspension • Cough • Respiratory Diseases

CALM-1: A 52-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (clinicaltrials.gov) - P3 | N=957 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Active, not recruiting ➔ Completed

Trial completion • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

A Study to Investigate the Difference In Blood Levels of Camlipixant Between Different Camlipixant Formulation Prototypes (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P1 trial • Cough • 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

BALANCE: A Study to Investigate Abdominal Symptoms With Camlipixant Compared With Placebo in Adults With Irritable Bowel Syndrome - Diarrhea (IBS-D) and Irritable Bowel Syndrome - Mixed (IBS-M) (clinicaltrials.gov) - P2 | N=420 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Disorder

CALM-2: A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough - China Extension (clinicaltrials.gov) - P3 | N=75 | Recruiting | Sponsor: GlaxoSmithKline

New P3 trial • Chronic Cough • Cough • 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

CALM-2: A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (clinicaltrials.gov) - P3 | N=975 | Active, not recruiting | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

BALANCE: A Study to Investigate Abdominal Symptoms With Camlipixant Compared With Placebo in Adults With Irritable Bowel Syndrome - Diarrhea (IBS-D) and Irritable Bowel Syndrome - Mixed (IBS-M) (clinicaltrials.gov) - P2 | N=420 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Gastrointestinal Disorder

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

The SOOTHE Trial of Camlipixant in RCC: A Cautionary Note on Stratification and Relevance. (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • Renal Cell Carcinoma

Reply to Zeng: The SOOTHE Trial of Camlipixant in RCC: A Cautionary Note on Stratification and Relevance. (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • Cough • Renal Cell Carcinoma • Respiratory Diseases

CALM-1: A 52-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (clinicaltrials.gov) - P3 | N=825 | Active, not recruiting | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2025 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

CALM-2: A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (clinicaltrials.gov) - P3 | N=975 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Trial completion date: Jun 2026 ➔ Apr 2027 | Trial primary completion date: Sep 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Reply to Rui and Chen: Initial Success: Camlipixant in Refractory Chronic Cough. (PubMed, Am J Respir Crit Care Med) - No abstract available

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

Initial Success: Camlipixant in Refractory Chronic Cough. (PubMed, Am J Respir Crit Care Med) - No abstract available

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

A Study of Camlipixant in Male and Female Healthy Participants and Participants With Hepatic Impairment Aged 18-75 Years of Age (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Bellus Health Inc. - a GSK company | N=21 ➔ 32

Enrollment change • Cough • Hepatology • 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

Effect of Camlipixant on Cardiac Repolarization in Healthy Participants: A Thorough QT/QTc Study (ATS 2025) - "Single 50 or 200 mg doses of camlipixant had no clinically meaningful effect on cardiac repolarization."

Clinical • Chronic Cough • Cough • Pain • Respiratory Diseases

Assessment of the Pharmacokinetics of BLU-5937 Extended Release Prototypes and a BLU-5937 Immediate Release Reference Formulation (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Bellus Health Inc. - a GSK company | N=14 ➔ 30

Enrollment change • Cough • Respiratory Diseases

Camlipixant: A New Hope for Refractory Chronic Cough? (PubMed, Am J Respir Crit Care Med) - No abstract available

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