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

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

Role of Monoclonal Antibodies in Patients With Eosinophilic Subtype COPD: A Meta-analysis of Randomized Controlled Trials (ATS 2024) - "Monoclonal antibodies ranged from Astegolimab, Benralizumab, Dupilumab, Itepekimab, and Mepolizumab. To conclude, in patients with eosinophilic subtype of COPD, the use of monoclonal antibodies led to a significant reduction in annualized exacerbation rate compared to standard of care. Monoclonal antibodies have an acceptable tolerability and safety profile."

Retrospective data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Safety Profile of Astegolimab, An Anti-ST2 Antibody: A Systematic Review (ATS 2024) - P2, P2b | "Astegolimab has been shown to be well tolerated in over 580 patients with asthma, atopic dermatitis, COPD, or COVID-19 pneumonia, with no safety concerns identified."

Clinical • Review • Asthma • Atopic Dermatitis • Cardiovascular • Chronic Obstructive Pulmonary Disease • Dermatitis • Dermatology • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • IL33

Post Hoc Analysis of Quantitative HRCT Imaging Parameters in Astegolimab (anti-ST2) Treated COPD Patients Associates Airway Wall Thickness With Clinical Outcomes (ATS 2024) - "These post-hoc analyses associate baseline airway wall thickness with poor outcomes in placebo treated subjects and suggest it enriches for anti-ST2 treatment benefit for FEV1. However, a major limitation of this study is sample size limiting statistical power and will need to be validated in appropriately powered prospective studies. Future work will investigate the longitudinal imaging changes to better understand therapeutic effects."

Clinical • Clinical data • Retrospective data • Chronic Obstructive Pulmonary Disease • Cough • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33

Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins. (PubMed, Eur J Intern Med) - "Two phase III randomized clinical trials (RCTs) showed a modest reduction in exacerbations in COPD patients with eosinophilic phenotype treated with mepolizumab (anti-IL-5) or benralizumab (anti-IL-5Rα). A phase III RCT showed a 30% reduction in exacerbations in COPD patients with ≥ 300 eosinophils/μL treated with dupilumab (anti-IL-4Rα)...Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD."

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

Mechanistic role of RND3-regulated IL33/ST2 signaling on cardiomyocyte senescence. (PubMed, Life Sci) - "NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) and ST2 antibody astegolimab treatments mitigated above effects...In contrast, RND3 overexpression in rats by injection of AAV9-CMV-RND3 particles inhibited IL33, ST2L, IL1α, IL6, and MCP1 expression in cardiac tissues, decreased serum IL33 levels, and increased sST2 levels. These results suggest that RND3 expression in cardiomyocytes modulates cell senescence by inhibiting the IL33/ST2/NF-κB signaling pathway, underscoring its potential as a therapeutic target in cardiovascular senescence."

Journal • Cardiovascular • Inflammation • Targeted Protein Degradation • IL1A • IL3 • IL33 • IL6

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

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

Approaches to COPD care: Targeting the ST2 receptor and IL-33 pathway as a potential option for patients at risk of exacerbating (ATS 2024) - "This educational event presents the latest scientific thinking in COPD care. Gain knowledge through educational presentations that bring to life: -The COPD patient: immunology, pathophysiology, and psychological burden -Astegolimab,* an investigational monoclonal antibody, potentially targeting the ST2 receptor and IL-33 pathway -The Genentech and Roche commitment to diversity in research *Astegolimab and its uses are investigational and have not been approved by the US Food and Drug Administration."

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

Astegolimab: NME submission in US for COPD in 2025 (Roche) - Q1 2024 Results: Regulatory submission in EU for COPD in 2025

BLA • European regulatory • Chronic Obstructive Pulmonary Disease • Immunology

Astegolimab: Data readout from P3 ARNASA trial (NCT05595642) for COPD in 2025 (Roche) - FY2023 Results

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

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. | Phase classification: P2b ➔ P2

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

Factors contributing to the nonlinear pharmacokinetics of astegolimab: a close examination of potential causes. (PubMed, Bioanalysis) - "Results & Our results demonstrate that there were two main contributors to PK nonlinearity: soluble target interference in the free PK assay, in addition to target-mediated drug disposition. Antidrug antibody status did not significantly impact PK."

Journal • PK/PD data

Astegolimab: NME submission in US for COPD in 2026 and beyond (Roche) - Q3 2023 Results: Regulatory submission in EU for COPD in 2026 and beyond

BLA • European regulatory • Chronic Obstructive Pulmonary Disease • Immunology

Effect of anti-ST2 on blood leukocyte and serum protein levels: insight from a phase IIa, placebo-controlled trial of astegolimab (COPD-ST2OP). (ERS 2023) - P2 | "Astegolimab strongly decreased blood eosinophils & an eosinophil-associated protein (CLC) but had negligible effect on other cells or proteins beyond its target, sST2.; Physiology; General respiratory patient care; Cell and molecular biology; Epidemiology"

Clinical • P2a data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

ALIENTO and ARNASA: Study designs of two randomised, double-blind, placebo-controlled trials of astegolimab in patients with COPD (ERS 2023) - P2b, P3 | "ALIENTO and ARNASA aim to establish the efficacy and safety of astegolimab in the treatment of patients with COPD.; Epidemiology; Pulmonary function testing; Pulmonary rehabilitation; Cell and molecular biology; Physiology; General respiratory patient care"

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

Heterogeneity of the lung microbiome influences response to Astegolimab, an anti ST2, in COPD (ERS 2023) - "Distinct lung microbiome features may inform the treatment benefit of Astegolimab for reducing COPD exacerbation frequency.; Epidemiology; Pulmonary function testing; Pulmonary rehabilitation; Cell and molecular biology; Physiology; General respiratory patient care"

Heterogeneity • Lung Microbiome • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • IL33

A Study to Evaluate the Long-Term Safety of Astegolimab in Participants With Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=2000 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

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

The Role of Biologics in Decreasing Asthma Exacerbation Rate: A Systematic Review and Meta-analysis (ATS 2023) - "Monoclonal antibodies targeting the Interleukin (IL)-5 pathway (Mepolizumab, Rezlizumab, Benralizumab), IL-4 receptor inhibitor (Dupilumab), Thymic stromal lymphopoietin inhibitor (Tezepelumab), IL-13 inhibitor (Tralinkinumab), IL-23 inhibitor (Risankizumab), and IL-33 inhibitor, (Astegolimab) have been studied in randomized controlled trials (RCTs)...Two RCTs compared Reslizumab to placebo, random effects standard difference of means was -0.359 (confidence interval -0.259 to -0.140, p value <0.0001)... Biologic agents have shown to significantly decrease the rate of annual asthma exacerbation rate compared to placebo."

Retrospective data • Review • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • IL23A • IL33 • IL4 • TSLP

A Study to Evaluate the Long-Term Safety of Astegolimab in Participants With Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=2000 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Astegolimab: NME submission in US for COPD in 2026 and beyond (Roche) - Q1 2023 Results: Regulatory submission in EU for COPD in 2026 and beyond

BLA • European regulatory • Chronic Obstructive Pulmonary Disease • Immunology