itepekimab (SAR440340) / Sanofi, Regeneron - LARVOL DELTA

A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Non-cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=300 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Press Release: Sanofi: strong Q1 performance and 2025 guidance confirmed (Sanofi Press Release) - "itepekimab (IL33 mAb)...The CEREN 1 (clinical study identifier: NCT06834347) and CEREN 2 (clinical study identifier: NCT06834360) phase 3 studies of two dose regimens of itepekimab compared with placebo as add-on therapy to intranasal corticosteroids in patients with inadequately controlled CRSwNP commenced dosing the first patient. A proof-of-concept phase 2 study (clinical study identifier: NCT06691113) of two dose regimens of itepekimab compared with placebo in patients with inadequately controlled chronic rhinosinusitis without nasal polyps commenced dosing the first patient."

Trial status • Chronic Rhinosinusitis With Nasal Polyps

Itepekimab: expanding clinical studies beyond COPD into chronic rhinosinusitis (GlobeNewswire) - "Itepekimab is currently being explored in patients with COPD in two phase 3 studies AERIFY-1 (clinical study identifier: NCT04701983) and AERIFY-2 (clinical study identifier: NCT04751487) with the readout anticipated in H2 2025, and in one phase 2 study, AERIFY-3 (clinical study identifier: NCT05326412), with the readout anticipated in H2 2025....Finally, itepekimab is being explored in a phase 2 study (clinical study identifier: NCT06280391) in bronchiectasis, with the readout anticipated in 2026."

P2 data • P3 data • Bronchiectasis • Chronic Obstructive Pulmonary Disease

From Mice To Humans: The Il-33 And Il-4rα Blocking Antibodies, Itepekimab And Dupilumab, Modulate Distinct And Common Inflammatory Mediators In Asthma (ATS 2025) - No abstract available

Preclinical • Asthma • Immunology • Respiratory Diseases • IL33

Sanofi launches Phase III clinical trial of subcutaneous IL-33 monoclonal antibody for chronic sinusitis in the country [Google translation] (Sina Corp) - "Itepekimab is the world's first subcutaneous IL-33 antibody drug to enter Phase III...This is the first time that the drug has started Phase III clinical trials for the treatment of chronic sinusitis, and it is also the first IL-33 antibody to enter Phase III for this indication...This is a randomized, double-blind, placebo-controlled, parallel-group, 52-week Phase III trial designed to evaluate the efficacy, safety, and tolerability of itepekimab in participants with poorly controlled chronic sinusitis with nasal polyps. The primary endpoint of the study was the change from baseline in endoscopic NPS and NCS at 24 weeks. A total of 102 institutions participated in the trial, with 33 participants planned to be enrolled in China and 210 participants planned to be enrolled internationally."

Trial status • Chronic Rhinosinusitis With Nasal Polyps

CEREN1: A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Sanofi

New P3 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

CEREN2: A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Sanofi

New P3 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Biologic Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. (PubMed, COPD) - "Benralizumab (RR 0.89 [95% CI 0.78 to 1]), itepekimab (RR 0.81 [95% CI 0.61 to 1.07]) and tezepelumab (RR 0.83 [95% CI 0.61 to 1.12]) may reduce exacerbations as compared to placebo (all low certainty). Dupilumab probably reduced exacerbations more than mepolizumab (RR 0.74 [95% CI 0.62 to 0.89]) (moderate certainty)...Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. Other biological therapies, including tezepelumab, have no important effect on patient-relevant outcomes."

Clinical • Journal • Retrospective data • Review • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Targeting alarmins in asthma- From the bench to the clinic. (PubMed, J Allergy Clin Immunol) - "Tezepelumab, an anti-TSLP antibody has already been approved for the treatment of severe asthma. In this review we discuss our current understanding of alarmin biology with a primary focus on allergic airway diseases. We link the mechanistic corollaries to the clinical implications and advances in drug development targeting alarmins-focusing on currently approved treatments, those under study, as well as future potential targets in the alarmin signaling pathways."

Journal • Review • Allergy • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33 • IL5

Regeneron Provides Business Updates and Highlights from Broad Clinical Pipeline at the 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Results are expected from the Phase 3 AERIFY study in the second half of 2025, with a potential BLA submission to follow...Phase 2 study testing combinations of tirzepatide and mibavademab is ongoing, with initial data expected from both in the second half of 2025."

P2 data • P3 data • Chronic Obstructive Pulmonary Disease • Obesity

AERIFY-3: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

AERIFY-3: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Sanofi | Trial completion date: Mar 2025 ➔ Aug 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Role of Monoclonal Antibodies in the Management of Eosinophilic COPD: A Meta-analysis of Randomized Controlled Trials. (PubMed, Ann Am Thorac Soc) - "In patients with eosinophilic COPD receiving standard of care therapy, the use of monoclonal antibodies led to a significant reduction in annualized COPD exacerbation rate compared to placebo. Monoclonal antibodies have an acceptable tolerability and safety profile."

Journal • Retrospective data • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review. (PubMed, Ther Adv Drug Saf) - "Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab)."

Journal • Review • Bronchiectasis • Cough • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD. (PubMed, ERJ Open Res) - P3 | "Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses."

Journal • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Tobacco Cessation • IL33

Pharmacokinetics of Subcutaneous Itepekimab Injection With an Autoinjector Device and Prefilled Syringe in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "The exposure was similar for both devices in each body weight and injection site subgroup. Overall, systemic exposure of 300-mg single-dose itepekimab in healthy participants was comparable when administered subcutaneously via an AI device and PFS, with an acceptable safety profile in both device groups."

Journal • PK/PD data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

Reduction in exacerbations with itepekimab in former smokers with chronic obstructive pulmonary disease (COPD) by prior exacerbation frequency (ERS 2024) - P2 | "Itepekimab significantly increased time to ECOPD and reduced the frequency of ECOPD in former smokers, irrespective of exacerbation history. These findings will be confirmed by further studies. Figure."

Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

The anti-IL-33 antibody, itepekimab, potently blocks airway inflammation post a single dose in mice (ERS 2024) - "Taken together, these results highlight that itepekimab is a potent blocker of IL-33 at doses as low as 1mg/kg, resulting in reduction of T1/T17 and T2 airway inflammation as well as lung remodeling in a chronic progressive lung inflammation mouse model."

Preclinical • Asthma • Chronic Obstructive Pulmonary Disease • Eosinophilia • Inflammation • Pneumonia • Respiratory Diseases • IL13 • IL1B • IL33 • IL4 • IL5 • TNFA

Latest Dupixent (dupilumab) and Itepekimab Data at ERS Highlight Scientific Innovation and Leadership in Respiratory Diseases (GlobeNewswire) - "These clinical and real-world abstracts presented in collaboration with Sanofi include four oral presentations and demonstrate the potential of targeting key drivers of type 2 inflammation and other pathways to address respiratory diseases, such as COPD and asthma, and improve patient outcomes...Among the notable Dupixent presentations at ERS is a pooled analysis of the previously reported Phase 3 BOREAS and NOTUS trials in uncontrolled COPD with evidence of type 2 inflammation...As shared in the abstract, the pooled analysis demonstrated that Dupixent patients (n=938) experienced a 31% reduction in the annualized rate of moderate or severe COPD exacerbations over 52 weeks compared to placebo (n=936; nominal p<0.0001)...Additionally, new research will be shared from the Phase 4 VESTIGE trial, a novel imaging study evaluating the effects of Dupixent on airway remodeling in certain adults with asthma."

P3 data • P4 data • Real-world • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases

Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate-to-severe atopic dermatitis: Results from two terminated phase II trials. (PubMed, Clin Transl Sci) - P2a, P2b | "Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL-33 may not be a key pathogenic driver in moderate-to-severe AD."

Clinical • Journal • P2 data • PK/PD data • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Dermatitis • Dermatology • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33

AERIFY-2: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=1210 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

AERIFY-1: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=960 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Study design of a phase 2, randomized, double-blind, placebo-controlled trial of Itepekimab in patients with non-cystic fibrosis bronchiectasis (WBC 2024) - No abstract available

Clinical • P2 data • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases