camlipixant (GSK5464714) / GSK - LARVOL DELTA

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

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