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UK-RES-2000248 Feb 2020

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UK-RES-2000003 Jan 2020

INTENDED FOR UK HEALTHCARE PROFESSIONALS
Trimbow® Logo - beclometasone/formoterol/glycopyrronium (87/5/9 mcg) Extrafine formulation
Background

Trimbow Evidence Summary

trimbow_subheader-mobile
The following Trimbow evidence summary provides you with information that will assist in your prescribing decision.

Indication[[1]]

Trimbow pMDI 87/5/9 is indicated for maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting β2-agonist or a combination of a long-acting β2-agonist and a long-acting muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see section 5.1 of the Trimbow SPC).1

Three compounds[[1]]

Beclometasone
Beclometasone given by inhalation is a corticosteroid with glucocorticoid anti-inflammatory action which suppresses inflammation in the lungs.1

Formoterol
Formoterol is a selective β2-adrenergic agonist that produces relaxation of bronchial smooth muscle in patients with reversible airways obstruction. The bronchodilating effect sets in rapidly, within 1–3 minutes after inhalation, and has a duration of 12 hours after a single dose.1

Glycopyrronium
Glycopyrronium is a high-affinity, long-acting muscarinic receptor antagonist (anticholinergic) resulting in a bronchodilator effect on the lungs.1

Trimbow clinical trials[[1-4]]

The Phase III clinical development programme in COPD included two 52-week active-controlled studies:1–3

  • TRILOGY compared Trimbow pMDI two inhalations twice daily, with Fostair (beclometasone/formoterol) 100/6 pMDI two inhalations twice daily (n=1,368 randomised patients). There were three co-primary endpoints:1,2
    • pre-dose FEV1
    • 2-h post-dose FEV1
    • transition dyspnoea index (TDI) focal score

    All were assessed at week 26. Superiority of Trimbow pMDI to Fostair pMDI 100/6 was met in change from baseline in pre-dose FEV1 (p<0.001), change from baseline in 2-h post-dose FEV1 (p<0.001), but unmet for TDI focal score (p=0.160).1,2

    A similar proportion of patients had treatment-emergent adverse events in the two treatment groups, with pneumonia reported in 3% of patients in both treatment arms. Most adverse events were mild or moderate in severity.2

  • TRINITY compared Trimbow two inhalations twice daily with Spiriva® HandiHaler® (tiotropium) one inhalation once daily, and with a free triple combination made up of Fostair 100/6 pMDI two inhalations twice daily plus Spiriva® HandiHaler® one inhalation once daily (n=2,691 randomised patients).1,3

    The primary endpoint showed that Trimbow pMDI resulted in a 20% (95% CI 8-31) reduction in the rate of moderate-to-severe COPD exacerbations compared with Spiriva® HandiHaler® alone at week 52 (p=0.0025; ARR 0.11).1,3

    Trimbow is not licensed as a step-up treatment option for COPD patients on a LAMA only.

    Trimbow is indicated for maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting β2-agonist or a combination of a long-acting β2-agonist and a long-acting muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see section 5.1 of the SPC).1

    A similar proportion of patients had adverse events in the three treatment groups. Most events were mild or moderate in severity. Pneumonia was reported in a small number of patients, with similar incidence in the three treatment groups (2–3%).3

Both studies were conducted in patients with a clinical diagnosis of COPD with severe to very severe airflow limitation (FEV1 less than 50% predicted) with symptoms assessed as a COPD Assessment Test (CAT®) score of 10 or above, and with at least one moderate or severe COPD exacerbation in the previous year.1–3

In addition, Trimbow was also studied vs. Ultibro® Breezhaler® (indacaterol/glycopyrronium) in a supporting Phase IIIb trial:1,4

  • TRIBUTE compared Trimbow two inhalations twice daily, with Ultibro® Breezhaler®, one inhalation once daily.1,4

    The primary endpoint was to compare Trimbow pMDI vs. Ultibro® Breezhaler® in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks (n=1,532 randomised patients). Trimbow pMDI resulted in a 15% reduction in the rate of moderate-to-severe COPD exacerbations compared with Ultibro® Breezhaler® (rate: 0.50 vs. 0.59 events per patient/year; p=0.043; ARR 0.09).1,4

    A similar proportion of patients had adverse events in the two treatment groups. Most events were mild or moderate in severity. Pneumonia was reported in a small number of patients, with similar incidence in the two treatment groups (4%).4

TRIBUTE was also conducted in patients with a clinical diagnosis of COPD with severe to very severe airflow limitation (FEV1 less than 50% predicted) with symptoms assessed as a COPD Assessment Test (CAT) score of 10 or above, and with at least one moderate or severe COPD exacerbation in the previous year.4

COPD exacerbations clinical trial summary[[1-4]]

For primary endpoints please see clinical trials section above.

  • Compared with Fostair 100/6 pMDI, Trimbow reduced the rate of moderate-to-severe exacerbations over 52 weeks by 23% (rate: 0.41 vs. 0.53 events per patient/year; p=0.005; ARR 0.12).1,2 This was a secondary endpoint of the TRILOGY study. For primary endpoints please see above.
  • Compared with Spiriva® HandiHaler®, Trimbow reduced the rate of moderate-to-severe exacerbations over 52 weeks by 20% (rate: 0.46 vs. 0.57 events per patient/year; p=0.0025; ARR 0.11)1,3
  • Compared with Spiriva® HandiHaler®, Trimbow also reduced the rate of severe exacerbations (i.e. excluding moderate exacerbations) by 32% (rate: 0.067 vs. 0.098 events per patient/year; p=0.017; ARR 0.03, secondary endpoint).1,3 For primary endpoints please see above.
  • No differences were observed when comparing Trimbow and the free triple combination of Fostair pMDI 100/6 plus Spiriva® HandiHaler® (moderate-to-severe exacerbation rate: 0.46 vs. 0.45 events per patient/year, secondary endpoint).1,3 For primary endpoints please see above.
  • In addition, compared with both Fostair 100/6 pMDI and with Spiriva® HandiHaler®, Trimbow significantly prolonged the time to first exacerbation (hazard ratio 0.80 and 0.84 respectively; p=0.020 and 0.015 respectively, secondary endpoint), with no differences between Trimbow and the free triple combination (hazard ratio 1.06, secondary endpoint).1,3 For primary endpoints please see above.
  • Compared with Ultibro® Breezhaler®, Trimbow reduced the rate of moderate-to-severe COPD exacerbations by 15% (rate: 0.50 vs. 0.59 events per patient/year; p=0.043; ARR 0.09)1,4

Effects on lung function (Pre-dose FEV[{1}])[[1-3]]

For primary endpoints please see clinical trials section above.

  • Compared with Fostair 100/6 pMDI, Trimbow significantly improved pre-dose FEV1 by 81mL after 26 weeks of treatment and by 63mL after 52 weeks of treatment (p<0.001, secondary endpoint).1,2 For primary endpoints please see above.
  • Compared with Spiriva® HandiHaler®, Trimbow significantly improved pre-dose FEV1 by 51mL after 26 weeks of treatment and by 61mL after 52 weeks of treatment (p<0.001, secondary endpoint).1,3 For primary endpoints please see above.
  • No differences were observed when comparing Trimbow and the free triple combination (p=0.85, difference of 3mL in pre-dose FEV1 after 52 weeks of treatment, secondary endpoint).1,3 For primary endpoints please see above.

Safety and tolerability[[2-6]]

      • TRILOGY safety and tolerability2,5

    • TRINITY safety and tolerability3,6

    • TRIBUTE safety and tolerability4

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Chiesi Limited on 0800 0092329 (UK) or PV.UK@Chiesi.com.