astegolimab (RG 6149) / Amgen, Roche - LARVOL DELTA

Therapeutic application of cytokine antagonists in chronic obstructive pulmonary disease (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "Biologics targeting type 2 inflammation, such as Tezepelumab (targeting thymic stromal lymphopoietin, TSLP), Itepekimab and Astegolimab (targeting IL-33), and Dupilumab (targeting IL-4/IL-13), have demonstrated potential in clinical trials to improve outcomes and enhance the quality of life for COPD patients. This article systematically outlines the molecular mechanisms of type 2 inflammation in COPD and the progress in targeted therapies. It emphasizes that the clinical translation of biologics must be guided by precision medicine, integrating mechanistic research with real-world evidence to advance COPD treatment towards "individualized intervention." Future research needs to further elucidate the interactions between type 2 and non-type 2 inflammatory phenotypes and to explore combination therapeutic strategies, in order to provide more comprehensive solutions for the prevention and management of COPD."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL33 • IL4 • IL5 • TSLP

Breaking new ground biologic in COPD: Beyond the usual puff (MTS 2025) - "The most significant advancement is the FDA approval of dupilumab, an anti-IL-4/IL-13 monoclonal antibody, for COPD patients with type 2 inflammation...Other biologics under investigation include anti-IL-5 agents like mepolizumab and benralizumab, which target eosinophilic inflammation, and anti-alarmins such as itepekimab, astegolimab, tozorakimab and tezepelumab, which interfere with epithelial-derived cytokines like IL-33 and TSLP...Biomarkers such as blood eosinophil count, FeNO, and mucus scoring techniques (CT-based and bronchoscopic) are becoming essential tools in identifying candidates for biologic therapy. This biologic revolution signals a departure from standard inhaler-based regimens, offering a new frontier in COPD management where therapy is matched to inflammatory phenotype—marking a bold step forward in precision respiratory medicine."

Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases • IL13 • IL33 • IL4 • IL5 • TSLP

Late Breaking Abstract - Randomised, placebo-controlled trial of astegolimab for COPD with frequent exacerbations: ALIENTO (ERS 2025) - No abstract available

Clinical • Late-breaking abstract • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

Comparable pharmacokinetics (PK), safety and tolerability of astegolimab administered subcutaneously (SC) via abdomen, thigh or upper arm: a Phase I, single-dose study (ERS 2025) - No abstract available

Clinical • PK/PD data • Asthma • Chronic Cough • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Cough • Immunology • Nasal Polyps • Pulmonary Disease • Respiratory Diseases

RCT Abstract - ARNASA: A Phase III randomised, double-blind, placebo-controlled trial of astegolimab for COPD with frequent exacerbations (ERS 2025) - No abstract available

Clinical • Late-breaking abstract • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

Electroacupuncture Protects Against Post-stroke Cognitive Impairment by Promoting an IL-33/ST2 Axis-Mediated Microglia M2 Polarization. (PubMed, Neurochem Res) - "To investigate the role of the Interleukin-33 (IL-33)/Interleukin 1 Receptor-Like 1 (ST2) signaling pathway in EA's therapeutic effects, the ST2 inhibitor Astegolimab (Anti-ST2) was stereotactically injected into the lateral ventricle prior to EA intervention...However, blockade of the IL-33/ST2 pathway with Anti-ST2 diminished the therapeutic benefits of EA, aggravated white matter injury and cerebral infarct volume, and amplified the inflammatory response. EA facilitates microglial polarization toward the M2 phenotype via the IL-33/ST2 signaling pathway, strengthens the structural integrity of cerebral white matter, and promotes neurological recovery after ischemic stroke."

Journal • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Inflammation • Ischemic stroke • IL10 • IL1B • IL33 • IL4 • IL6 • TNFA

A Study to Evaluate the Efficacy and Safety of Astegolimab in Participants With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2 | N=1334 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed

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

Genentech Provides Update on Astegolimab in Chronic Obstructive Pulmonary Disease (Businesswire) - P3 | N=1,290 | ARNASA (NCT05595642) | Sponsor: Hoffmann-La Roche | "...the Phase III ARNASA study did not meet its primary endpoint of a statistically significant reduction in the AER, demonstrating a numerical 14.5% reduction at 52 weeks when astegolimab was given every two weeks. The results were generally consistent across secondary endpoints...The total number of exacerbations was lower than prospectively anticipated [in the trial]....The safety profile of astegolimab was consistent with previously reported data, with no new safety signals identified."

P3 data: top line • Chronic Obstructive Pulmonary Disease

Genentech Provides Update on Astegolimab in Chronic Obstructive Pulmonary Disease (Businesswire) - P2b | N= 1,334 | ALIENTO (NCT05037929) | Sponsor: Genentech, Inc | "Genentech...announced today topline results...The pivotal Phase IIb ALIENTO study met its primary endpoint and showed that astegolimab reduced the annualized exacerbation rate (AER) by a statistically significant 15.4% at 52 weeks, when given every two weeks...The results were generally consistent across secondary endpoints; The total number of exacerbations was lower than prospectively anticipated [in the trial]."

P2b data • Chronic Obstructive Pulmonary Disease

Advancements in Biologic Therapies for Pediatric Asthma: Emerging Therapies and Future Directions. (PubMed, Cureus) - "Biologics such as omalizumab, mepolizumab, dupilumab, benralizumab, and tezepelumab have been reported to reduce severe asthma exacerbations, with reassuring short-term safety profiles among children and adolescents (pediatrics)...Literature review also highlights the emerging treatment regimens for non-T2 endotypes, such as tezepelumab, ecleralimab, and astegolimab (IL-33), which influence both T2 and non-T2 pathways...Ultimately, the continued advancement and strategic implementation of biologic therapies hold the potential to revolutionize the management of severe pediatric asthma, leading to reduced exacerbations and corticosteroid use, improved quality of life, and more precise treatment strategies tailored to individual patient profiles. Moreover, future research should continue to address the challenges related to long-term safety, cost-effectiveness, and equitable access, which are vital to realizing the true potential of biologic therapies in treating pediatric..."

Journal • Review • Asthma • Immunology • Inflammation • Pediatrics • Pulmonary Disease • Respiratory Diseases • IL33

Structural Basis for Inhibition of IL-33 Induced ST2 Activation by Astegolimab (ATS 2025) - "Biochemical and biophysical studies using recombinantly generated proteins show that astegolimab prevents IL33 from binding to ST2 in solution. A 2.6 Å cryo-EM structure of ST2 bound to the Fab fragment from astegolimab reveals that astegolimab binds to the IL33-binding interface on ST2, directly competes with IL33 binding, thereby prevents formation of the active signaling complex necessary for ST2 activation."

Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL1RAP • IL33

Serum Soluble ST2 (sST2) Is Associated With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations and Enhanced Treatment Response to Astegolimab (Anti-ST2) (ATS 2025) - P2, P2b, P3 | "In the LEUKO study (NCT00493974), hospitalized COPD patients experiencing acute exacerbations received zileuton to assess the effect on hospital stay length. Our post-hoc analyses indicate sST2 levels: 1) are prognostic for exacerbations in placebo-treated COPD subjects, when measured at baseline, and 2) are elevated at the time of hospitalized exacerbation, suggesting NFκB signaling cytokines, such as IL-33, underlie COPD exacerbations. Notably, both COPD and asthma subjects with higher levels of sST2 at baseline derived greater astegolimab AERR treatment benefit."

Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33 • ST2

Biologic Therapies for Severe Asthma: Current Insights and Future Directions. (PubMed, J Clin Med) - "The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP)...Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration."

Journal • Review • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • IL13 • IL33 • IL4 • IL5

Astegolimab: NME submission in US for COPD in 2025 (Roche) - Q1 2025 Results: Regulatory submission in EU for COPD in 2025

EMA filing • FDA filing • Chronic Obstructive Pulmonary Disease • Immunology

ARNASA: A Study to Evaluate Astegolimab in Participants With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P3 | N=1290 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2025 ➔ Dec 2026

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

A Study to Evaluate the Effect of Injection Site on PK of Astegolimab in Healthy Subjects (clinicaltrials.gov) - P1 | N=78 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Oct 2024 | Trial primary completion date: Apr 2025 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date

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

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

Astegolimab: Data from P2 ALIENTO trial (NCT05037929) for COPD in 2025 (Roche) - Bernstein's 23rd Annual Pan European Premium Review Conference: Data from P3 ARNASA trial (NCT05595642) for COPD in 2025

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

Astegolimab: Data from P3 ARNASA trial (NCT05595642) for COPD in 2025 (Roche) - Q3 2024 Results

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

Astegolimab: NME submission in US for COPD in 2025 (Roche) - Q3 2024 Results: Regulatory submission in EU for COPD in 2025

EMA filing • FDA filing • Chronic Obstructive Pulmonary Disease • Immunology

Pharmacokinetics (PK) of the anti-ST2 monoclonal antibody, astegolimab (ERS 2024) - P2, P2b, P3 | "Baseline sST2 levels were comparable in healthy volunteers and patients with asthma or COPD. PK in patients with COPD will be confirmed in pivotal studies (NCT05037929; NCT05595642)."

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

A Study to Evaluate the Effect of Injection Site on PK of Astegolimab in Healthy Subjects (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Evaluate the Efficacy and Safety of Astegolimab in Participants With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2 | N=1440 | Recruiting | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Recruiting

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

A Study to Evaluate the Effect of Injection Site on PK of Astegolimab in Healthy Subjects (clinicaltrials.gov) - P1 | N=78 | Recruiting | Sponsor: Genentech, Inc.

New P1 trial