Menu

Inhaled molecules for COPD treatment

How does molecule pharmacology correlate with clinical efficacy and safety?

Pharmacological properties of inhaled respiratory molecules are critical to ensure the best possible clinical outcomes.

  • Pharmacological summary of inhaled molecules

      Name Onset of action1-6 Duration of action3,4,6-11 Bioavailability*4,9,11-15 Selectivity5,6
    Muscarinic antagonist Umeclidinium 5–15 min 26–28 h 13% M3/M2 T½ ratio: 9
    Tiotropium 30 min ~24 h 19.5% M3/M2 T½ ratio: 10
    Glycopyrronium ~20 min 24 h 40% M3/M2 T½ ratio: 16
    β2 agonist Vilanterol ~6 min ~24 h 27% β2/β1: 2400; β2/β3: 1000
    Salmeterol ~15 min ~12 h N/A β2/β1: 3000; β2/β3: 2100
    Indacaterol ~4 min ~24 h 43–45% β2/β1: 16; β2/β3: 20
    Formoterol ~4 min 8–12 h N/A β2/β1: 150; β2/β3: 59
    Inhaled corticosteroid Fluticasone furoate N/A N/A 15% N/A
    Budenoside 10 min N/A 39% N/A
    Beclomethasone N/A N/A 62% N/A

    *Absolute bioavailability for all apart from fluticasone furoate (inhaled bioavailability) and budesonide (absolute systemic bioavailability).

Umeclidinium, vilanterol and fluticasone furoate were developed to allow for once-daily dosing, with high selectivity and low systemic exposure to minimise side effects.

The pharmacological properties of these inhaled respiratory molecules have translated into clinical efficacy and safety with single-inhalation, once-daily dosing.

Click a molecule to learn more about the pharmacology

chemical-structure-of-umeclidinium

LAMA

Umeclidinium (UMEC)

GO TO UMECLIDINIUM (UMEC)

chemical-structure-of-vilanterol

LABA

Vilanterol (VI)

GO TO VILANTEROL (VI)

chemical-structure-of-fluticasone-furoate

ICS

Fluticasone furoate (FF)

GO TO FLUTICASONE FUROATE (FF)

Learn more about head-to-head studies of inhaled combination therapies

LEARN MORE

Umeclidinium (UMEC)

Head-to-head comparison of UMEC via Ellipta versus TIO via HandiHaler

PREV
NEXT

UMEC was superior to TIO for trough FEV1 at Day 85.16

graph-showing-the-least-squares-mean-change-from-baseline-in-trough-FEV1-at-day-85-with-UMEC-and-TIO.-UMEC-improved-trough-FEV1-by-154-ml-and-TIO-by-95-ml,-with-a-treatment-difference-of-59-ml-for-UMEC-compared-with-TIO-in-the-per-protocol-population

*Delivered dose for UMEC 55 μg. Superiority margin: 0 mL. FEV1 MCID = 100 mL.17

UMEC and TIO had a similar safety profile.16

The most common adverse events in both treatment groups were:

  • Headache (UMEC: n=30 [6%]; TIO: n=32 [6%])
  • Nasopharyngitis (UMEC: n=27 [5%]; TIO: n=23 [5%])
On-treatment events, n (%)
 UMEC (n=509)
 TIO (n=508)
Adverse events 165 (32)
 153 (30)
Non-fatal serious adverse events 17 (3)
 14 (3)
Fatal serious adverse events 0 2 (<1)
Drug-related adverse events 17 (3) 8 (2)

Adapted with permission from Feldman G, Maltais F, Khindri S, et al. A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 μg compared with tiotropium 18 μg in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:719-730.

Coverage over the dosing interval

Adapted with permission from Feldman G, Maltais F, Khindri S, et al. A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 μg compared with tiotropium 18 μg in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:719-730.

Pharmacology of UMEC

chemical-structure-of-umeclidinium-highlighting-key-chemical-features-that-confer-high-selectivity-for-M3-over-M2-receptors-in-the-lungs-and-rapid-inactivation-upon-systemic-exposure-limiting-potential-side-effects,-as-well-as-high-affinity-and-long-lasting-binding-to-M3-receptors-in-the-lungs

UMEC is a LAMA that blocks the bronchoconstrictor effects of acetylcholine on M3 muscarinic receptors expressed in airway smooth muscle.21

Pharmacology summary

Name
 Onset of action2-5
 Duration of action3,4,8,9
 Bioavailability*4,9,12,15 Selectivity5
Umeclidinium 5–15 min 26–28 h 13% M3/M2 T½ ratio: 9
Tiotropium 30 min ~24 h 19.5% M3/M2 T½ ratio: 10
Glycopyrronium ~20 min 24 h 40% M3/M2 T½ ratio: 16

*Absolute bioavailability.

Vilanterol (VI)

Coverage over the dosing interval

24-h serial FEV1 on Day 1 and Day 28.22

VI is not licensed in COPD as a monotherapy; FEV1 MCID = 100 mL.17 Adapted with permission from Hanania NA, Feldman G, Zachgo W, et al. A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 μg compared with tiotropium 18 μg in patients with COPD. Chest. 2012;142:119-127.

Pharmacology of VI

chemical-structure-of-vilanterol-highlighting-key-chemical-features-that-confer-a-rapid-onset-and-24-hour-duration-of-action,-leading-to-a-clinical-benefit-of-greater-than-24-hour-bronchodilation,-as-well-as-high-selectivity-for-β2-over-β1-receptors-and-rapid-inactivation-upon-systemic-exposure-limiting-potential-side-effects

VI is a LABA that stimulates β2-adrenergic receptors to antagonise bronchoconstriction and relax airway smooth muscle.21

Pharmacology summary

VI has a high potency and high selectivity for β2 over β1 receptors.6

  Potency (pEC50)6
 Onset t1/2 (min)6
 Selectivity ratio (β2 / β1)6
 Duration of action6,7,10,11
 Bioavailability*11,13
Vilanterol
 8.62 ± 0.27
 5.8 ± 0.5*
 2400 ~24 h 27%
Salmeterol
 6.84 ± 0.03
 15.2 ± 0.6
 3000
 ~12 h
 N/A
Indacaterol
 6.84 ± 0.16
 4.0 ± 0.2†
 16‡
 ~24 h
 43–45%
Formoterol 8.56 ± 0.18 4.0 ± 0.1† 150‡ 8–12 h N/A

‡

*Absolute bioavailability; †P<0.0001 vs salmeterol; ‡P<0.0001 vs vilanterol. In vitro data. VI is not licensed in COPD as a monotherapy.

Fluticasone furoate (FF)

Therapeutic index of FF in patients with asthma

Relationship between airway protection and systemic activity for FF, FP and BUD.25

Therapeutic index data based on pharmacological outcomes; direct clinical outcomes not established. Red arrows indicate the therapeutic index at the corresponding ICS dose. AMP PC20 is a measure of airway protection from ICS and corresponds to the provocative concentration of AMP that results in a 20% drop in FEV1. Cortisol suppression is an indicator of systemic activity; 20% cortisol suppression is close to the lower boundary of detectable systemic exposure for corticosteroids, after which systemic adverse events become more likely.14 The patient population included patients with asthma not COPD; 54 patients were randomized to treatment. FF is not licensed in COPD as a monotherapy. Adapted with permission from Daley-Yates P, Brealey N, Thomas S, et al. Therapeutic index of inhaled corticosteroids in asthma: A dose-response comparison on airway hyperresponsiveness and adrenal axis suppression. Br J Clin Pharmacol. 2021;87:483-493.

Tables adapted with permission from Daley-Yates P, Brealey N, Thomas S, et al. Therapeutic index of inhaled corticosteroids in asthma: A dose-response comparison on airway hyperresponsiveness and adrenal axis suppression. Br J Clin Pharmacol. 2021;87:483-493. AMP, adenosine monophosphate; BUD, budesonide; CI, confidence interval; ED, effective dose; FF, fluticasone furoate; FP, fluticasone propionate; ICS, inhaled corticosteroid; PC, provocative concentration; TI, therapeutic index.

Anti-inflammatory effect of FF/VI in patients with asthma

Continued airway anti-inflammatory effects* were seen for 3 days post last dose of FF/VI.26

Anti-inflammatory effect of FF/VI in patients with asthma

*As assessed by FeNO; FeNO was used as the primary measure to monitor the anti-inflammatory activity of FF/VI as it is a validated biomarker of Type 2 inflammation in asthma and highly sensitive to ICS therapy. Patient population was steroid naive and not current smokers to assess FeNO suppression. Patients received FF/VI 100/25 µg or placebo once daily for 14 days, followed by a 21-day washout period. Adapted with permission from Bardsley G, Daley-Yates P, Baines A, et al. Anti-inflammatory duration of action of fluticasone furoate/vilanterol trifenatate in asthma: a cross-over randomised controlled trial. Respir Res. 2018;19:133.

Pharmacology of FF

chemical-structure-of-fluticasone-furoate- highlighting-key-chemical-features-that-confer-rapid-inactivation-upon-systemic-exposure,-limiting-potential-side-effects,-and-high-receptor-binding-for-sustained-efficacy

FF is an ICS that binds to glucocorticoid receptors to reduce the number of inflammatory cells in airways.27,28

PREV
NEXT

Different receptor binding affinities of ICSs.14

graph-showing-the-different-receptor-binding-affinities-of-ICSs-relative-to-dexamethasone,-where-dexamethasone-affinity-is-100:-2989-for-fluticasone-furoate,-1775-for-fluticasone-propionate,-1345-for-beclomethasone-dipropionate-and-935-for-budesonide

FF is not licensed in COPD as a monotherapy. Glucocorticoid receptor binding affinity is relative to dexamethasone where dexamethasone affinity = 100.

Different bioavailabilities* of ICSs.14

graph-showing-the-different-absolute-bioavailabilities-of-ICSs:-15-percent-for-fluticasone-furoate,-16-percent-for-fluticasone-propionate,-62-percent-for-beclomethasone-dipropionate-and-39-percent-for-budesonide

FF is not licensed in COPD as a monotherapy. *Absolute bioavailability.

How does the pharmacology of inhaled molecules relate to clinical efficacy of LAMA/LABA therapies?

Head-to-head comparison of UMEC/VI via Ellipta versus TIO/OLO via Respimat

PREV
NEXT

UMEC/VI was non-inferior* and superior† to TIO/OLO for trough FEV1 at Week 8 in the per protocol and ITT populations, respectively.29

graph-showing-least-squares-mean-change-from-baseline-in-trough-FEV1-at-week-8-with-UMEC/VI-and-TIO/OLO.-UMEC/VI-improved-trough-FEV1-by-180-ml-and-TIO/OLO-by-128-ml,-with-a-treatment-difference-of-52-ml-for-UMEC/VI-compared-with-TIO/OLO-in-the-ITT-population

*Non-inferiority margin set at -50 mL. †Superiority margin set at 0 mL. FEV1 MCID = 100 mL.17

Change from baseline in CAT score with UMEC/VI and TIO/OLO at Week 8.29

bar-graph-showing-least-squares-mean-change-from-baseline-in-CAT-score-at-week-8-with-UMEC/VI-and-TIO/OLO.-UMEC/VI-improved-CAT-score-by-1.38-units-and-TIO/OLO-by-1.26-units,-with-a-treatment-difference-of-minus-0.11-units-for-UMEC/VI-compared-with-TIO/OLO-in-the-ITT-population

CAT MCID = 2 units.30

UMEC/VI and TIO/OLO had similar safety profiles.29

The most frequently reported adverse events were upper respiratory tract infections (UMEC/VI: n=11 [5%]; TIO/OLO: n=14 [6%]).

Events, n (%)
 UMEC/VI (n=235)
 TIO/OLO (n=230)
Adverse events 59 (25) 71 (31)
Non-fatal serious adverse events 3 (1)
 2 (<1)
Fatal serious adverse events 0 0

Do improvements in lung function correlate with other clinical benefits?

PREV
NEXT

Improvements in lung function are associated with improvements in patient outcomes – results from a pooled analysis (n=23,213 patients).31

graph-showing-the-relationship-between-FEV1-and-SGRQ-indicating-that-improvements-in-lung-function-are-associated-with-improvements-in-SGRQ

Model-based analysis by treatment. Thin lines represent model predictions; thick lines and point represent patient population for a given treatment (median and 50% PI of FEV1 change for treatment class). Improvements in FEV1 explain part of the efficacy of bronchodilator treatment on PROs. Adapted with permission from Donohue JF, Jones PW, Bartels C, et al. Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2018;49:11-19.

Improvements in lung function are associated with improvements in patient outcomes – results from a pooled analysis (n=23,213 patients).31

graph-showing-the-relationship-between-FEV1-and-TDI-indicating-that-improvements-in-lung-function-are-associated-with-improvements-in-TDI

Model-based analysis by treatment. Thin lines represent model predictions; thick lines and point represent patient population for a given treatment (median and 50% PI of FEV1 change for treatment class). Improvements in FEV1 explain part of the efficacy of bronchodilator treatment on PROs. Adapted with permission from Donohue JF, Jones PW, Bartels C, et al. Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2018;49:11-19.

Improvements in lung function are associated with improvements in patient outcomes – results from a pooled analysis (n=23,213 patients).31

graph-showing-the-relationship-between-FEV1-and-exacerbation-rates-indicating-that-improvements-in-lung-function-are-associated-with-a-reduction-in-exacerbation-rates

Model-based analysis by treatment. Thin lines represent model predictions; thick lines and point represent patient population for a given treatment (median and 50% PI of FEV1 change for treatment class). Improvements in FEV1 explain part of the efficacy of bronchodilator treatment on PROs. Adapted with permission from Donohue JF, Jones PW, Bartels C, et al. Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2018;49:11-19.

Improvements in lung function are associated with improvements in patient outcomes – results from a pooled analysis (n=23,213 patients).31

graph-showing-the-relationship-between-FEV1-and-rescue-medication-use-indicating-that-improvements-in-lung-function-are-associated-with- a-reduction-in-rescue-medication-use

Model-based analysis by treatment. Thin lines represent model predictions; thick lines and point represent patient population for a given treatment (median and 50% PI of FEV1 change for treatment class). Improvements in FEV1 explain part of the efficacy of bronchodilator treatment on PROs. Adapted with permission from Donohue JF, Jones PW, Bartels C, et al. Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2018;49:11-19.

Head-to-head study of UMEC/VI DPI versus GLY/FOR MDI: AERISTO

AERISTO was a 24-week randomised, double-blind, double-dummy, parallel-group, multicentre, non-inferiority study in 1119 patients with symptomatic moderate-to-very severe COPD.32

Co-primary endpoints were change from baseline in trough FEV1 and peak change from baseline in 2-h post-dose FEV1 over 24 weeks.

PREV
NEXT

For trough FEV1, a co-primary endpoint of the AERISTO study, GLY/FOR did not achieve non-inferiority to UMEC/VI.32

graph-showing-least-squares-mean-change-from-baseline-in-trough-FEV1-at-week-24-with-GLY/FOR-and-UMEC/VI.-GLY/FOR-improved-trough-FEV1-by-82-ml-and-UMEC/VI-by-170-ml,-with-a-treatment-difference-of-minus-87-ml-for-GLY/FOR-compared-with-UMEC/VI-in-the-per-protocol-population

Non-inferiority margin set at -50 mL.32 FEV1 MCID = 100 mL.17

For the other co-primary endpoint of peak change from baseline in FEV1 within 2 h post-dosing, GLY/FOR was non-inferior to UMEC/VI.32

graph-showing-least-squares-mean-change-peak-change-in-FEV1-at-2-hours-post-dosing-at-week-24-with-GLY/FOR-and-UMEC/VI.-GLY/FOR-improved-peak-FEV1-by-294-ml-and-UMEC/VI-by-297-ml,-with-a-treatment-difference-of-minus-3-ml-for-GLY/FOR-compared-with-UMEC/VI-in-the-per-protocol-population

Non-inferiority margin set at -50 mL.32

Change from baseline in CAT score with UMEC/VI and GLY/FOR.32

graph-showing-least-squares-mean-change-from-baseline-in-CAT-score-at-week-24-with-GLY/FOR-and-UMEC/VI.-GLY/FOR-improved-CAT-score-by-2.95-units-and-UMEC/VI-by-3.51-units,-with-a-treatment-difference-of-0.56-units-for-GLY/FOR-compared-with-UMEC/VI-in-the-ITT-population

CAT MCID = 2 units.30

Change from baseline in TDI score with UMEC/VI and GLY/FOR.32

graph-showing-least-squares-mean- TDI-focal-score-at-week-24-with-GLY/FOR-and-UMEC/VI.-GLY/FOR-improved-TDI-by-1.2-units-and-UMEC/VI-by-1.6-units,-with-a-treatment-difference-of--0.37-units-for-GLY/FOR-compared-with-UMEC/VI-in-the-ITT-population

TDI MCID = 1 unit.33

UMEC/VI and GLY/FOR had similar safety profiles.32 The most common adverse event in both treatment groups was headache (UMEC/VI: n=41 [7%]; GLY/FOR: n=34 [6%]).

Treatment-emergent adverse events, n (%)
 UMEC/VI (n=552)
 GLY/FOR (n=552)
Adverse events 248 (45)
 226 (41)
Serious adverse events 40 (7)
 32 (6)
Fatal serious adverse events 3 (<1) 3 (<1)
Drug-related adverse events 3 (<1) 7 (1)

Adapted with permission from Maltais F, Ferguson GT, Feldman GJ, et al. A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD. Adv Ther. 2019;36:2434-2449.

How does the pharmacology of inhaled molecules relate to clinical efficacy of ICS-containing therapies?

Real-world effectiveness of FF/VI via Ellipta compared with usual care in patients with COPD (Salford Lung Study).34

PREV
NEXT

Moderate/severe exacerbations rates with FF/VI versus usual care.34

graph-showing-least-squares-mean-annual-rate-of-moderate-severe-exacerbations-with-FF/VI-and-usual-care.-Annual-exacerbation-rates-were-1.74-with-FF/VI-and-1.90-with-usual-care,-correponding-to-a-8.4%-reduction-in-exacerbation-rates-for-FF/VI-compared-with-usual-care

Usual care defined as physician’s free choice of LAMA and/or LABA (14%), or an ICS-containing regimen (86%; 54% of patients were on triple therapy).

FF/VI had a similar safety profile to usual care, including incidence of pneumonia serious adverse events.34

Treatment-emergent adverse events, n (%)
 FF/VI (n=1396)
 Usual care (n=1403)
Serious adverse events
 404 (29)
 383 (27)
Pneumonia SAESI
 94 (7)
 83 (6)
Fatal serious adverse events
 45 (3)
 30 (2)

Usual care defined as physician’s free choice of LAMA and/or LABA (14%), or an ICS-containing regimen (86%; 54% of patients were on triple therapy).

Efficacy and safety of FF/UMEC/VI via Ellipta compared with multiple-inhaler triple therapy in patients with COPD

Two replicate 12-week, Phase IV, randomised, double-blind, triple-dummy, parallel-group, multicentre, non-inferiority trials evaluated the efficacy and safety of FF/UMEC/VI single-inhaler triple therapy versus BUD/FOR + TIO multiple-inhaler triple therapy in 1460 patients with symptomatic moderate-to-very severe COPD.35

The primary endpoint was the weighted mean change from baseline in FEV1 over 0–24 h at Week 12.

PREV
NEXT

Once-daily FF/UMEC/VI was non-inferior to BUD/FOR + TIO for the primary endpoint of weighted mean change from baseline in 0–24-h FEV1 at Week 12.35

graph-showing-least-squares-mean-change-from-baseline-in-weighted-mean-FEV1-over-0-to-24-hours-at-week-12-with-FF/UMEC/VI-and-BUD/FOR-plus-TIO.-Both-treatments-improved-weighted-mean-FEV1,-with-a-treatment-difference-of-14-ml-for-FF/UMEC/VI-compared-with-BUD/FOR-plus-TIO-in-the-ITT-population-pooled-analysis

Non-inferiority margin set at -50 mL. Superiority margin set at 10 mL. Adapted with permission from Ferguson GT, Brown N, Compton C, et al. Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials. Respir Res. 2020;21:131.

Change from baseline in trough FEV1 at Day 84 with FF/UMEC/VI versus BUD/FOR+TIO.35

graph-showing-least-squares-mean-change-from-baseline-in-trough-FEV1-at-day-84-with-FF/UMEC/VI-and-BUD/FOR-plus-TIO.-Trough-FEV1-increased-with-FF/UMEC/VI-and-decreased-with-BUD/FOR-plus-TIO,-with-a-treatment-difference-of-56-ml-for-FF/UMEC/VI-compared-with-BUD/FOR-plus-TIO-in-the-ITT-population-pooled-analysis

Adapted with permission from Ferguson GT, Brown N, Compton C, et al. Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials. Respir Res. 2020;21:131.

Pooled analysis of serial FEV1 at Week 12.35

graph-showing-pooled-analysis-of-least-squares-mean-change-from-baseline-in-serial-FEV1-at-week-12-with-FF/UMEC/VI-and-BUD/FOR-plus-TIO.-Timepoints-of-12-and-24-hours-are-highlighted-to-note-the-greater-improvement-in-FEV1-for-FF/UMEC/VI-compared-with-BUD/FOR-plus-TIO

Adapted with permission from Ferguson GT, Brown N, Compton C, et al. Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials. Respir Res. 2020;21:131.

FF/UMEC/VI had a similar safety profile to BUD/FOR + TIO, including incidence of pneumonia.35

Treatment-emergent adverse events, n (%)
 FF/UMEC/VI (n=729)
 BUD/FOR + TIO (n=731)
Adverse events 223 (31) 230 (31)
Serious adverse events
 37 (5)
 31 (4)
Pneumonia AESI 7 (1) 9 (1)
Fatal serious adverse events 0 (0) 1 (<1)

The recording of AEs was limited to treatment-related AEs, SAEs and AEs leading to study treatment discontinuation or study withdrawal.

Real-world effectiveness of FF/UMEC/VI via Ellipta compared with non-Ellipta multiple-inhaler triple therapy

INTREPID was a 24-week, multicentre, randomised, open-label, phase IV effectiveness study comparing once-daily FF/UMEC/VI single-inhaler triple therapy delivered by the Ellipta inhaler with any licenced non-Ellipta MITT in 3092 patients with COPD in a usual clinical practice setting in five European countries.36 The primary effectiveness outcome was the proportion of responders based on the CAT score at Week 24.

PREV
NEXT

Percentage of responders according to CAT score at Week 24 with FF/UMEC/VI versus non-ELLIPTA MITT in a usual clinical care setting.36

graph-showing-percentage-of-patients-achieving-a-clinically-meaningful-CAT-response-at-week-24-with-FF/UMEC/VI-and-non-Ellipta-MITT.-The-proportion-of-responders-was-47-percent-with-FF/UMEC/VI-and-40-percent-with-non-Ellipta-MITT,-and-the-proportion-of-non-responders-was-49-percent-with-FF/UMEC/VI-and-54-percent-with-non-Ellipta-MITT,-corersponding-to-an-OR-of-1.31-for-FF/UMEC/VI-versus-non-Ellipta-MITTat-week-24.-Three-percent-of-patients-on-FF/UMEC/VI-and-6-percent-on-non-Ellipta-MITT-had-a-missing-CAT-score

CAT response defined as a decrease in CAT score of ≥2 units from baseline.36 Adapted with permission from Halpin DMG, Worsley S, Ismaila AS, et al. INTREPID: single- versus multiple-inhaler triple therapy for COPD in usual clinical practice. ERJ Open Res. 2021;7:00950-2020.

Change from baseline in trough FEV1 at Week 24 with FF/UMEC/VI versus non-ELLIPTA MITT in a usual clinical care setting.36

graph-showing-least-squares-mean-change-from-baseline-in-trough-FEV1-at-week-24-with-FF/UMEC/VI-and-non-Ellipta-MITT.-Both-treatment-improved-trough-FEV1-with-a-treatment-difference-of-53-ml-for-FF/UMEC/VI-compared-with-non-Ellipta=MITT

FEV1 MCID = 100 mL.17

FF/UMEC/VI had a similar safety profile to non-ELLIPTA MITT in a usual clinical care setting, including incidence of pneumonia.36

Treatment-emergent adverse events, n (%)
 FF/UMEC/VI (n=1545)
 Non-ELLIPTA MITT (n=1547)
Adverse events
 250 (16)
 151 (10)
Serious adverse events
 114 (7)
 114 (7)
Pneumonia SAESI
 27 (2)
 32 (2)
Fatal serious adverse events
 8 (<1)
 8 (<1)

Summary

gsk-ung-icon

UMEC, VI and FF have been developed for single-inhalation, once-daily dosing

gsk-graph-icon

Head-to head trials and real-world studies have demonstrated improvement in patient outcomes with UMEC, UMEC/VI, FF/VI and FF/UMEC/VI versus other combination therapies with similar safety profiles

Abbreviations

Δ, difference; AESI, adverse event of special interest; AMP, adenosine-5'-monophosphate; BID, twice daily; BUD, budesonide; CAT, COPD Assessment Test; CFB, change from baseline; CI, confidence interval; COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; ED, effective dose; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; FF, fluticasone furoate; FP, fluticasone propionate; FOR, formoterol; GLY, glycopyrronium; ICS, inhaled corticosteroid; ITT, intent-to-treat; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; LS, least square; MCID, minimum clinically important difference; MDI, metered dose inhaler; MITT, multiple-inhaler triple therapy; N/A, not available; OLO, olodaterol; PC, provocative concentration; pEC50, negative logarithm of the half maximal effective concentration; PI, prediction interval; PRO, patient reported outcome; QD, once-daily; SAESI, serious adverse event of special interest; SGRQ, St George’s Respiratory Questionnaire; T1/2, half-life; TDI, transition dyspnoea index; TI, therapeutic index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol

Ellipta is owned by or licensed to the GSK Group of Companies. HandiHaler and Respimat are registered trademarks of Boehringer Ingelheim International GmbH.

References

  1. Budesonide. https://go.drugbank.com/drugs/DB01222. Accessed May 2021.
  2. Umeclidinium. https://www.medicine.com/drug/umeclidinium/hcp. Accessed May 2021.
  3. Babu KS, Morjaria JB. Ther Adv Chronic Dis. 2017;8(4-5):81-91.
  4. Koumis T, Samuel S. Clin Ther. 2005;27(4):377-392.
  5. Prakash A, Babu KS, Morjaria JB. Drug Discov Today. 2013;18(21-22):1117-1126.
  6. Slack RJ, Barrett VJ, Morrison VS, et al. J Pharmacol Exp Ther. 2013;344(1):218-230.
  7. Formoterol Fumarate. https://www.sciencedirect.com/topics/medicine-and-dentistry/formoterol-fumarate. Accessed May 2021.
  8. Glycopyrronium Bromide. https://www.sciencedirect.com/topics/medicine-and-dentistry/glycopyrronium-bromide. Accessed May 2021.
  9. Tiotropium Bromide. https://www.sciencedirect.com/topics/medicine-and-dentistry/tiotropium-bromide. Accessed May 2021.
  10. Salmeterol. https://www.medicine.com/drug/salmeterol/hcp. Accessed May 2021.
  11. Slaton RM, Cruthirds DL. P T. 2012;37(2):86-98.
  12. Glycopyrronium. https://go.drugbank.com/drugs/DB00986. Accessed May 2021.
  13. Vilanterol. https://go.drugbank.com/drugs/DB09082. Accessed May 2021.
  14. Daley-Yates PT. Br J Clin Pharmacol. 2015;80(3):372-380.
  15. GlaxoSmithKline. INCRUSE® ELLIPTA® Product Information. https://au.gsk.com/media/375066/incruse_ellipta_pi_au_007_approved.pdf. Accessed May 2021.
  16. Feldman G, Maltais F, Khindri S, et al. Int J Chron Obstruct Pulmon Dis. 2016;11:719-730.
  17. Donohue JF. COPD. 2005;2(1):111-124
  18. Lainé DI. Expert Rev Clin Pharmacol. 2010;3(1):43-53.
  19. Lainé DI, McCleland B, Thomas S, et al. J Med Chem. 2009;52(8):2493-2505.
  20. Salmon M, Luttmann MA, Foley JJ, et al. J Pharmacol Exp Ther. 2013;345(2):260-270.
  21. GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2021. Available at: https://goldcopd.org/2021-gold-reports/ [accessed March 2021].
  22. Hanania NA, Feldman G, Zachgo W, et al. Chest. 2012;142(1):119-127.
  23. Kempsford R, Norris V, Siederer S. Pulm Pharmacol Ther. 2013;26(2):256-264.
  24. Procopiou PA, Barrett VJ, Bevan NJ, et al. J Med Chem. 2010;53(11):4522-4530.
  25. Daley-Yates P, Brealey N, Thomas S, et al. Br J Clin Pharmacol. 2021;87(2):483-493.
  26. Bardsley G, Daley-Yates P, Baines A, et al. Respir Res. 2018;19(1):133.
  27. Biggadike K, Bledsoe RK, Hassell AM, et al. J Med Chem. 2008;51(12):3349-3352.
  28. Barnes PJ. Pharmaceuticals (Basel). 2010;3(3):514-540.
  29. Feldman GJ, Sousa AR, Lipson DA, et al. Adv Ther. 2017;34(11):2518-2533.
  30. Kon SS, Canavan JL, Jones SE, et al. Lancet Respir Med. 2014;2(3):195-203.
  31. Donohue JF, Jones PW, Bartels C, et al. Pulm Pharmacol Ther. 2018;49:11-19.
  32. Maltais F, Ferguson GT, Feldman GJ, et al. Adv Ther. 2019;36(9):2434-2449.
  33. Mahler DA, Witek TJ, Jr. COPD. 2005;2(1):99-103.
  34. Vestbo J, Leather D, Diar Bakerly N, et al. N Engl J Med. 2016;375(13):1253-1260.
  35. Ferguson GT, Brown N, Compton C, et al. Respir Res. 2020;21(1):131.
  36. Halpin DMG, Worsley S, Ismaila AS, et al. ERJ Open Res. 2021;7(2).

© 2022 GSK group of companies or its licensor. Trade marks are owned by or licensed to the GSK group of companies.

NX-GBL-UCV-WCNT-210002 | Date of preparation: August 2022