Efficacy & Safety

 

 

 

 

KRONOS study design

 

BID, twice daily; BUD, budesonide; DPI, dry powder inhaler; FORM, formoterol; GLY, glycopyrrolate; MDI, metered-dose inhaler.
aThe BUD/FORM MDI product evaluated in KRONOS is not currently licensed in any market.
bAll patients received salbutamol sulphate for rescue use as needed.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758.

 

 

Baseline patient demographics in KRONOS (mITT Population)1

mITT, modified intent-to-treat; SD, standard deviation.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758.

 

 

BREZTRI powerfully protects symptomatic patients from moderate to severe exacerbations vs GLY/FORM in a majority of patients without a recent exacerbation history1-3

 

aBREZTRI vs GLY/FORM MDI: Annual rates: 0.46 vs 0.95 (RR 0.48, 95% CI 0.37–0.64; p<0.0001).1,2 bBREZTRI vs BUD/FORM MDI: Annual rates 0.46 vs 0.56 (RR 0.82; 95% CI 0.58–1.17; p=0.2792).1,2
1. BREZTRI AEROSPHERE SmPC; 2. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758; 3. Data on File, AstraZeneca Veeva Approval ID: REF-54777.

 

 

BREZTRI significantly reduces COPD hospitalisations vs GLY/FORM1

aBREZTRI vs GLY/FORM MDI: Annual rates: 0.05 vs 0.13 (RR 0.36, 95% CI 0.18–0.70; unadjusted p=0.0026).1 The p-value is unadjusted because it was not included in the Type 1 error control plan for the KRONOS study.2 bBREZTRI vs BUD/FORM MDI: Annual rates 0.05 vs 0.05 (RR 0.85; 95% CI 0.34–2.13; p=0.7363).1
1. Data on File, AstraZeneca Veeva Approval ID: REF-54777; 2. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758. Supplementary Appendix.

 

 

BREZTRI: Fast onset within 5 minutes1a

aBREZTRI AEROSPHERE is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms. 2 bTime to onset is defined as the first post-dose time point where the mean change from baseline in FEV1 exceeded 100 mL.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758; 2. BREZTRI AEROSPHERE SmPC.

 

 

BREZTRI provides powerful and sustained improvements in lung function1,2

1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758; 2. BREZTRI AEROSPHERE SmPC.

 

 

BREZTRI significantly improves lung function as measured by FEV1 AUC1

AUC, area under the curve.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758.

 

 

BREZTRI works fast to improve lung function, while reducing symptoms and improving quality of life vs dual therapies1-4abc

aBREZTRI AEROSPHERE is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms.2 b175 mL improvement from baseline FEV1 at 5 minutes post-dose with BREZTRI.1,2 cSGRQ total score over 24 weeks with BREZTRI vs BUD/FORM MDI (-1.38; p<0.0001); BREZTRI vs GLY/FORM MDI (-1.62; p<0.0001).3
1. Ferguson GT et al. Lancet Respir Med. 2018;6(10):747-758; 2. BREZTRI AEROSPHERE SmPC; 3. Martinez FJ et al. Am J Respir Crit Care Med. 2020;201:A5073; 4. Rabe KF et al. Am J Respir Crit Care Med. 2020;201:A2493.

 

 

BREZTRI safety profile in KRONOS1a

URTI, upper respiratory tract infection.
aThe percentages of patients with confirmed (by a Clinical Endpoint Committee) pneumonia were as follows: BUD/GLY/FORM, 1.9%; GLY/FORM, 1.6%; BUD/FORM MDI, 1.9%; BUD/FORM DPI, 1.3%.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758.

 

 

ETHOS study design

aScreening period of 1-4 weeks could be extended to 10 weeks if a patient experienced a COPD exacerbation in order to allow for treatment and recovery. bRandomization was stratified by exacerbation history (1 or ≥2 moderate/severe exacerbations), post-bronchodilator FEV1 (25% to <50% or 50 to <65% predicted), blood eosinophil count (<150 or ≥150 cells/mm3), and country. cThe BUD/GLY/FORM 160 MDI product and BUD/FORM MDI product evaluated in ETHOS are not currently licensed in any market. dAll patients received salbutamol sulphate for rescue use as needed.
1. Rabe KF et al. Respir Med. 2019;158:59-66; 2. Rabe KF et al. N Engl J Med. 2020;383:35-48.

 

 

Baseline patient demographics in ETHOS (mITT Population)

aIn the safety population.
1. Rabe KF et al. N Engl J Med. 2020;383:35-48; 2. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary appendix.

 

 

BREZTRI powerfully protects symptomatic patients with a recent exacerbation history from moderate to severe exacerbations vs dual therapies in a symptomatic patient population1

aBREZTRI vs GLY/FORM MDI: Annual rates: 1.08 vs 1.42 (RR 0.76, 95% CI 0.69–0.83; p<0.001). bBREZTRI vs BUD/FORM MDI: Annual rates 1.08 vs 1.24 (RR 0.87; 95% CI 0.79–0.95; p=0.003).1
1. Rabe KF et al. N Engl J Med. 2020;383:35-48.

 

 

BREZTRI significantly reduces COPD hospitalisations vs BUD/FORM1

aBREZTRI vs GLY/FORM MDI: Annual rates: 0.13 vs 0.16 (RR 0.80, 95% CI 0.66–0.97; p=0.02). bBREZTRI vs BUD/FORM MDI: Annual rates 0.13 vs 0.15 (RR 0.84; 95% CI 0.69–1.03; p=0.09).
1. Rabe KF et al. N Engl J Med. 2020;383:35-48.

 

 

BREZTRI reduced the risk of on- and off-treatment all-cause mortality by 49% vs GLY/FORM1

aBREZTRI vs GLY/FORM MDI: HR 0.51, 95% CI 0.33-0.80; unadjusted p=0.0035.1 P-value is considered unadjusted due to an endpoint in the Type I error control testing hierarchy not reaching significance.2 bBREZTRI vs BUD/FORM MDI: HR 0.72, 95% CI 0.44–1.16; p=0.1721.1 cResults shown include additional data from 354 patients who had incomplete 1-year vital status at the time of trial completion.1,3 dThe percentages of patient deaths included in the time to death analysis in each arm were as follows: BUD 320/GLY/FORM, 1.4%; GLY/FORM, 2.6%; BUD/FORM, 1.9%.1
1. Martinez FJ, et al. Am J Respir Crit Care Med. 2021;203(5):553-56; 2. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary Appendix; 3. Rabe KF et al. N Engl J Med. 2020;383:35-48.

 

 

BREZTRI powerfully reduces symptoms of COPD and improves quality of life1,2

*BREZTRI significantly reduced rescue albuterol sulfate use over 24 weeks by –0.51 puffs/day vs LAMA/LABA pMDI (mean change from baseline –1.2 vs –0.7; p<0.0001) and by –0.37 puffs/day vs ICS/LABA pMDI (mean change from baseline –1.2 vs –0.8; p<0.0001) in patients with a history of ≥1 puff/day at baseline.9,15
SGRQ, St. George’s Respiratory Questionnaire.
1. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary Appendix; 2. Martinez FJ et al. Am J Respir Crit Care Med. 2020;201:A5073.

 

 

BREZTRI significantly improves COPD symptoms, reducing the need for rescue medication vs dual therapies1,2

aRescue medication user population.
1. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary Appendix; 2. Rabe KF et al. Am J Respir Crit Care Med. 2020;201:A2493.

 

 

BREZTRI consistently reduced risk of death vs GLY/FORM in all datasets1

Note: All treatments were administered BID. ITT population.
aSignificant p-values (ie, <0.046) in the original dataset are unadjusted due to an endpoint in the Type I error control testing hierarchy not reaching significance; bP-values were not adjusted for multiplicity; cThe on-treatment analysis included deaths that occurred within 30 days of the last day of treatment.
1. Martinez FJ, et al. Am J Respir Crit Care Med. 2021;203(5):553-56.

 

 

BREZTRI mortality benefit seen across many subgroups and analyses1

1. Martinez FJ, et al. Am J Respir Crit Care Med. 2021;203(5):553-56.

 

 

Powerful protection of BREZTRI1-5

aBREZTRI vs GLY/FORM and BUD/FORM.1-3 bBREZTRI vs GLY/FORM MDI: HR 0.51, 95% CI 0.33–0.80; unadjusted p=0.0035.5 P-value is considered unadjusted due to an endpoint in the Type I error control testing hierarchy not reaching significance.6
1. BREZTRI AEROSPHERE SmPC; 2. Ferguson GT et al. Lancet Respir Med. 2018;6(10):747-758; 3. Rabe KF et al. N Engl J Med. 2020;383:35-48; 4. Data on File, AstraZeneca Veeva Approval ID: REF-54777; 5. Martinez FJ, et al. Am J Respir Crit Care Med. 2021;203(5):553-56; 6. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary Appendix.

 

 

BREZTRI mortality benefit vs GLY/FORM was not driven by an early period of acute ICS withdrawal effect in patients using ICS at study entry

Note: All treatments were administered BID. ITT population.
1. Martinez FJ, et al. Am J Respir Crit Care Med. 2021;203(5):553-56.

 

 

BREZTRI safety profile in ETHOS1,2

aThe percentages of patients with confirmed pneumonia were as follows: BREZTRI, 4.2%; GLY/FORM, 2.3%; BUD/FORM, 4.5%; confirmation was obtained from an independent Clinical Endpoint Committee.
1. Rabe KF et al. N Engl J Med. 2020;383:35-48; 2. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary Appendix.

 

 

BREZTRI safety profile

aBudesonide, glycopyrronium, and formoterol fumarate.
1. Rabe KF et al. N Engl J Med. 2020;383:35-48; 2. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758; 3. Data on File, AstraZeneca Veeva Approval ID: REF-54777.

 

 

KRONOS and ETHOS baseline demographics (mITT population)

aReversible defined as improvement in FEV1 of ≥12% and ≥200 mL after albuterol administration compared with before albuterol.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758; 2. Rabe KF et al. N Engl J Med. 2020;383:35-48; 3. Rabe KF et al. N Engl J Med. 2020;383:35-48. Supplementary Appendix.

 

 

Two Phase 3 studies: KRONOS and ETHOS study populations

BD, bronchodilator; FVC, forced vital capacity.
aIncluded scheduled SABAs and/or SAMAs.
1. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758; 2. Ferguson GT et al. Lancet Respir Med. 2018;6:747-758.
Supplementary Appendix; 3. Rabe KF et al. Respir Med. 2019;158:59-66; 4. Rabe KF et al. N Engl J Med. 2020;383:35-48.

 

 

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