Breztri Aerosphere (budesonide/formoterol fumarate/glycopyrronium) / AstraZeneca - LARVOL DELTA

COMPARING PATIENT ADHERENCE AND PERSISTENCE TO SINGLE-INHALER TRIPLE THERAPY VS MULTIPLE-INHALER TRIPLE THERAPY: A NARRATIVE REVIEW OF REAL-WORLD OBSERVATIONAL STUDIES (CHEST 2024) - "In the US study, patients were included if they initiated SITT with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or MITT... Differences in reimbursement timelines, practice patterns, and data completeness within the included studies introduces a large amount of heterogeneity between studies. Nonetheless, despite these regional and methodological differences, consistently better adherence and persistence with SITT versus MITT was observed at 12 months post-initiation of the study period in these studies. CLINICAL IMPLICATIONS: These data support the GOLD 2024 recommendations1 and suggest a consistent benefit in adherence and persistence with SITT compared with MITT for patients with COPD, irrespective of regional differences."

Adherence • Clinical • Observational data • Real-world • Real-world evidence • Review • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

REDUCED RISK OF CARDIOPULMONARY EVENTS FOR COPD PATIENTS INITIATING BUDESONIDE/GLYCOPYRROLATE/FORMOTEROL VS MULTIPLE INHALER TRIPLE THERAPY IN THE US: THE SKOPOS-MAZI STUDY (CHEST 2024) - "Compared with patients treated with MITT, BGF was associated with a lower risk of severe cardiopulmonary events. This study provides real-world evidence for the reduction of such events with BGF and supports optimization of patients with COPD using BGF instead of MITT. CLINICAL IMPLICATIONS: A multidisciplinary understanding of cardiopulmonary risk is required."

Clinical • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Heart Failure • Immunology • Ischemic stroke • Myocardial Infarction • Respiratory Diseases

EFFECTIVENESS OF BUDESONIDE/GLYCOPYRROLATE/FORMOTEROL FUMARATE IN CHINESE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN REAL-WORLD CLINICAL PRACTICE (CHEST 2024) - P | "Continuous improvements in health status at week 4 to 12 and an increase in lung function at week 12 following the initiation of BGF were observed in this COPD real-world study.Acknowledgements/Disclosure Statement: This study was funded by AstraZeneca China. The authors have no conflicts of interest. CLINICAL IMPLICATIONS: These real-world findings supported the use of BGF as an efficacious therapy for patients with COPD."

Clinical • Real-world • Real-world evidence • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Assess PT010 in Adult and Adolescent Participants With Inadequately Controlled Asthma (LOGOS) (clinicaltrials.gov) - P3 | N=2178 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Assess PT010 in Adult and Adolescent Participants With Inadequately Controlled Asthma (KALOS) (clinicaltrials.gov) - P3 | N=2212 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Lung Exposure Bioequivalence of Budesonide, Glycopyrronium, & Formoterol (BGF) Metered Dose Inhaler (MDI) Hydrofluoroolefin (HFO) With a Spacer (Treatment B), BGF MDI Hydrofluoroalkane (HFA) With a Spacer (Treatment A), as Well as BGF MDI HFO Without a Spacer (Treatment C) (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: AstraZeneca | N=132 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

RECORD: REported Outcomes in COPD With Trixeo in Real worlD in Germany (clinicaltrials.gov) - P=N/A | N=475 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Patient reported outcomes • Real-world • Real-world evidence • Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Late Breaking Abstract - Prompt initiation of budesonide/glycopyrronium/formoterol reduces exacerbations and cardiopulmonary events in patients with COPD (MITOS EROS+CP study) (ERS 2024) - "Promptly initiating BGF was associated with 24% and 32% fewer subsequent AECOPD and 12.3% and 9.3% fewer severe CP events compared with delayed and very delayed groups. Proactive disease management with BGF may be warranted to prevent future AECOPD and CP events among patients with COPD."

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

Late Breaking Abstract - Promptly escalating to budesonide/glycopyrronium/formoterol from dual therapy reduces exacerbations and cardiopulmonary events in patients with COPD (MITOS EROS+CP study) (ERS 2024) - "Promptly escalating to BGF from dual therapy was associated with 23% and 31% fewer subsequent AECOPD and 19% and 13% fewer CP events compared with delayed and very delayed groups. Proactive disease management with BGF may be warranted to prevent future AECOPD and cardiopulmonary events among patients with COPD."

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

Characteristics of patients with COPD treated with Budesonide/Glycopyrronium/Formoterol in the real world; The RECORD Study (ERS 2024) - "The main reason for initiating BGF in the RECORD COPD population was ongoing symptoms despite inhaled therapy, indicating the unmet need of pts with moderate/severe COPD. Study funded by AstraZeneca"

Clinical • Real-world • Real-world evidence • Asthma • Cardiovascular • Chronic Obstructive Pulmonary Disease • Cough • Diabetes • Dyslipidemia • Hypertension • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases

Real-world outcomes of Budesonide/Glycopyrronium/Formoterol therapy in COPD after 3 months; Interim analysis of the RECORD study (ERS 2024) - "Interim data suggests pts experience improvements in PRO scores and lung function at M3 following BGF. Study funded by AstraZeneca"

Clinical • Real-world • Real-world evidence • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Efficacy of Budesonide/Glycopyrronium/Formoterol FDC across blood eosinophil ranges in Indian COPD patients: post-hoc analysis of a phase-IV clinical-trial (ERS 2024) - "Findings of this post-hoc analysis suggest that benefits of triple therapy are not restricted to patients with high BEC even in Indian population. 1. E-poster-NAPCON, Hyderabad, Nov30 - Dec3,2023"

Clinical • P4 data • Retrospective data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Real-world safety of budesonide/glycopyrrolate/formoterol in Chinese patients with chronic obstructive pulmonary disease (ERS 2024) - P | "Mean AMPQ total score was 20.6 (full score 25). Conclusions BGF MDI was safe and well-tolerated in real-world clinical practice and most patients were satisfied with the device."

Clinical • Real-world • Real-world evidence • Chronic Obstructive Pulmonary Disease • Dysphonia • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Initiation of single- and multiple-inhaler triple therapy for COPD and adoption of budesonide/glycopyrrolate/formoterol (BGF): pooled analysis from the AURA Germany study (ERS 2024) - "TT is generally initiated in COPD patients who are inadequately controlled and symptomatic. BGF initiators tended to have greater clinical burden vs. other TT initiators and may indicate a preference to try newer therapies for these patients."

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

Initiation of single- and multiple-inhaler triple therapy for COPD and adoption of budesonide/glycopyrrolate/formoterol (BGF): insights from primary care in England - the AURA UK study (ERS 2024) - "Often TT initiators experience symptoms and exacerbations while on dual therapy. Patients initiating BGF tended to have greater clinical burden vs. other TT initiators which may indicate prescriber preference to explore additional therapies to adequately manage their condition."

Clinical • Asthma • Cardiovascular • Chronic Obstructive Pulmonary Disease • CNS Disorders • Depression • Immunology • Obstructive Sleep Apnea • Psychiatry • Pulmonary Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Single-inhaler triple therapy improves small airway dysfunction in moderate to severe asthma. (ERS 2024) - " Subjects included 30 asthma patients who switched from ICS/LABA to SITT (fluticasone furoate/vilanterol/umeclinidium, mometasone/indacaterol/glycopyrronium, and budesonide/formoterol/glycopyrronium), with spirometry and oscillometry performed before and after switching... SITT improved SAD, and higher R5−R20 before SITT predicted responsiveness to SITT in moderate to severe asthma patients. Table. Multivariate logistic regression analyses for predicting responders to SITT Adjusted odds ratio 95% confidence interval P-value ACT 0.242 0.049 to 1.190 0.080 History of smoking 0.173 0.024 to 1.260 0.083 R5−R20(per 0.01 cmH2O/L/s) 1.130 1.010 to 1.260 0.037 Fres 0.526 0.2070 to 1.340 0.178"

Asthma • Immunology • Respiratory Diseases

AstraZeneca announces the completion of the clinical programme to support the transition of Breztri to next-generation propellant with near-zero Global Warming Potential (AstraZeneca Press Release) - "AstraZeneca has completed the studies that support the first regulatory filings for the transition of Breztri/Trixeo Aerosphere (budesonide/glycopyrronium/formoterol fumarate or BGF) to an innovative, next-generation propellant with 99.9% lower Global Warming Potential than propellants used in currently available inhaled medicines. Breztri is a triple-combination therapy for chronic obstructive pulmonary disease (COPD) and will be the first medicine in AstraZeneca’s portfolio of pressurised-metered dose inhalers (pMDIs) to transition to the new propellant...Results from the studies for Breztri with the next-generation propellant will be shared with regulatory authorities, with first submissions in Europe, the UK and China expected before the end of 2024."

China filing • EMA filing • MHRA filing • Trial completion • Asthma • Chronic Obstructive Pulmonary Disease • Immunology

Effect of Triple Therapy on Cardiovascular and Severe Cardiopulmonary Events in COPD: A Post-hoc Analysis of a Randomized, Double-Blind, Phase 3 Clinical Trial (ETHOS). (PubMed, Am J Respir Crit Care Med) - P3 | "In the Phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality versus dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF)...Measurements and Main BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for CVAESI (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate-to-very severe COPD."

Clinical • Journal • P3 data • Retrospective data • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

RECORD: REported Outcomes in COPD With Trixeo in Real worlD (clinicaltrials.gov) - P=N/A | N=148 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

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

Comparison table: Inhaled drugs for treatment of COPD. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Drugs for COPD. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Tobacco Cessation

Effect of the Inhaled Triple Therapies Over the Small Airway in Biomass Exposure (clinicaltrials.gov) - P4 | N=128 | Recruiting | Sponsor: National Institute of Respiratory Diseases, Mexico

New P4 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Benefits of budesonide/glycopyrronium/formoterol fumarate dihydrate on lung function and exacerbations of COPD: a post-hoc analysis of the KRONOS study by blood eosinophil level and exacerbation history. (PubMed, Respir Res) - P3 | "These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations."

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

INDOS-B: Post-marketing Phase 4 Safety & Tolerability Study of Breztri aerosphereTM in Indian Patients With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P4 | N=150 | Not yet recruiting | Sponsor: AstraZeneca

New P4 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

H1 and Q2 2024 results (AstraZeneca Press Release) - "Total Revenue of $3,791m from R&I medicines increased 19% (22% at CER) and represented 15% of overall Total Revenue (H1 2023: 14%). This reflected growth in Fasenra, Tezspire, Breztri, Saphnelo and Airsupra, following its recent launch....Combined sales of Tezspire, recorded by Amgen and AstraZeneca, amounted to $507m in H1 2024 (H1 2023: $257m)."

Sales • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Lupus • Respiratory Diseases • Systemic Lupus Erythematosus