camlipixant (GSK5464714) / GSK - LARVOL DELTA

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

Evaluation of the Potential Drug-drug Interactions Between Gemfibrozil or Dabigatran Etexilate and Camlipixant (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Bellus Health Inc. - a GSK company | N=32 ➔ 45

Enrollment change • Cough • 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=21 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Completed | N=32 ➔ 21

Enrollment change • Trial completion • Cough • Hepatology • Respiratory Diseases

Camlipixant in Refractory Chronic Cough: A Phase 2b, Randomized, Placebo-controlled Trial (SOOTHE). (PubMed, Am J Respir Crit Care Med) - P2b | " Camlipixant treatment reduced cough frequency and improved patient reported outcomes in patients with refractory chronic cough, with an acceptable safety profile. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT04678206."

Journal • P2b data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Camlipixant in Refractory Chronic Cough: A Phase 2a, Randomized, Controlled Trial (RELIEF). (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • P2a data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

The Impact of Paroxetine, a Strong CYP2D6 Inhibitor, on the Pharmacokinetics and Safety of Camlipixant in Healthy Participants (AAAAI-WAO 2025) - "The total exposure of a single camlipixant dose was comparable when administered alone or with paroxetine. The co-administration of camlipixant with CYP2D6 inhibitors is not expected to affect camlipixant pharmacokinetics."

Clinical • PK/PD data • Chronic Cough • Cough • Pain • Respiratory Diseases

The Impact of Itraconazole, a Strong CYP3A4 Inhibitor, on the Pharmacokinetics and Safety of Camlipixant in Healthy Participants (AAAAI-WAO 2025) - "The observed drug–drug interaction is not considered clinically significant. The co-administration of camlipixant with CYP3A4 inhibitors is not expected to affect camlipixant pharmacokinetics."

Clinical • PK/PD data • Chronic Cough • Constipation • Cough • Gastroenterology • Gastrointestinal Disorder • Respiratory Diseases

A Study to Investigate the Effect of Food on Camlipixant Concentrations in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Completed

Trial completion • Cough • Respiratory Diseases

Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist. (PubMed, J Biol Chem) - "Our findings also demonstrate that conformational changes in the upper-body domain, including the turret and camlipixant-binding pocket, play a critical role: turret opening facilitates P2X3 channel closure to a radius of 0.7 Å, hindering cation transfer, while turret closure leads to channel opening. Structural and functional studies combined with molecular dynamics simulations provide a comprehensive understanding of camlipixant's selective inhibition of P2X3, offering a foundation for future drug development targeting this receptor."

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

Evaluation of the Effect of Rifampin and Rabeprazole on the Pharmacokinetics of Camlipixant (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Bellus Health Inc. - a GSK company | N=32 ➔ 42

Enrollment change • Cough • Respiratory Diseases

Camlipixant: Data from P3 CALM-1 trial (NCT05599191) for refractory chronic cough in H2 2025 (GSK) - Q3 2024 Results: Data from P3 CALM-2 trial (NCT05600777) for refractory chronic cough in H2 2025

P3 data • Chronic Cough • Cough

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 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial primary completion date • Cough • Hepatology • Respiratory Diseases

DESIGN OF THE LANDMARK CALM-1 AND CALM-2 PHASE 3 CLINICAL TRIALS OF CAMLIPIXANT IN REFRACTORY CHRONIC COUGH (CHEST 2024) - P3 | "The CALM-1 and CALM-2 trials will evaluate efficacy, safety, and tolerability of camlipixant in a broad population of patients with RCC (including UCC) utilizing a run-in period and novel stratification by cough frequency. CLINICAL IMPLICATIONS: The novel design features of the CALM-1 and CALM-2 trials offer the potential for improved assessment of benefit/risk in the population of patients with greatest unmet clinical need. Given the absence of any available treatment indicated for RCC in the USA, the CALM-1 and CALM-2 trials will provide evidence of the efficacy and safety of a potentially novel treatment option for patients with RCC (including UCC)."

Clinical • P3 data • Chronic Cough • Cough • Immunology • Respiratory Diseases

Determination of Camlipixant (BLU-5937) P2X3 antagonist activity in a sensory neuronal model and bronchial epithelial cells (ERS 2024) - "Both PNEs and PBECs express functional P2X3 receptors. Camlipixant acted as a potent P2X3 antagonist of receptor excitation in both cell types."

Chronic Cough • Cough • Respiratory Diseases

Prior and concomitant medication use in patients with refractory chronic cough: post-hoc analysis of SOOTHE (ERS 2024) - P2b | " SOOTHE (NCT04678206) was a randomised, multi-centre, double-blind, placebo-controlled, parallel arm, dose-finding study of camlipixant for RCC treatment... Despite CM use for underlying conditions, pts had inadequate control of their cough, largely unrelated to age or gender."

Clinical • Retrospective data • Asthma • Chronic Cough • Cough • Gastroenterology • Gastroesophageal Reflux Disease • Immunology • Respiratory Diseases

A Study to Investigate the Effect of Food on Camlipixant Concentrations in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Not yet recruiting ➔ Recruiting

Enrollment open • Cough • Respiratory Diseases

Camlipixant: Data from P3 CALM-1 trial (NCT05599191) for refractory chronic cough in 2025 (GSK) - Q2 2024 Results: Data from P3 CALM-2 trial (NCT05600777) for refractory chronic cough in 2025

P3 data • Chronic Cough

Camlipixant: Acceptance of regulatory submissions in US/EU for refractory chronic cough (based on CALM-1 and CALM-2 trials) in H2 2025 (GSK) - Q2 2024 Results

EMA filing • FDA filing • Chronic Cough

Assessment of the Pharmacokinetics of BLU-5937 Extended Release Prototypes and a BLU-5937 Immediate Release Reference Formulation (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Completed | N=32 ➔ 14

Enrollment change • Trial completion • Cough • Respiratory Diseases

A Study to Investigate the Effect of Food on Camlipixant Concentrations in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P1 trial • Cough • Respiratory Diseases

A Second Drug Binding Site in P2X3. (PubMed, bioRxiv) - "P2X3 binds to camlipixant at a previously unidentified drug-binding site and functions as an allosteric inhibitor. Structure-activity studies combined with modeling and simulations have shed light on the mechanisms underlying the selective targeting and inhibition of P2X3 by camlipixant, distinguishing it from other members of the P2X receptor family."

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