Prescribing information

 

       

Indication: ENERZAIR® BREEZHALER® is indicated as a maintenance treatment for asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid, who experienced one or more asthma exacerbations in the previous year.1
 

Once-daily ENERZAIR®BREEZHALER® is the first LABA/LAMA/ICS fixed-dose combination in the EU for the treatment of these patients.1–4

Two Phase III trials* have assessed the safety and efficacy of ENERZAIR® BREEZHALER® – IRIDIUM and ARGON – and their results are presented below. 

 

 3,5,6

IRIDIUM is a phase III, multicentre, randomized, double-blind, parallel-group study, designed to compare the efficacy and safety of QVM149 (ENERZAIR® BREEZHALER®) with QMF149 (ATECTURA® BREEZHALER®) (indacaterol acetate/mometasone furoate inhalation powder) in patients with asthma.

The purpose of the trial was to evaluate the efficacy and safety of two different doses of ENERZAIR® BREEZHALER® (150/50/80 µg and 150/50/160 µg) versus two respective ATECTURA® BREEZHALER® doses (150/160 µg and 150/320 µg) in patients with uncontrolled asthma, as determined by pulmonary function testing and effects on asthma control.

Primary endpoint: Demonstrate superiority in trough FEV1 of ENERZAIR® BREEZHALER® high-dose vs. ATECTURA® BREEZHALER® high-dose after 26 weeks.

Key secondary endpoint: Demonstrate superiority in ACQ-7 score with ENERZAIR® BREEZHALER® high-dose vs. ATECTURA® BREEZHALER® high-dose after 26 weeks.

 4,7

ARGON (NCT03158311) is a phase IIIb, multicentre, randomized, 24-week, parallel-group, non-inferiority, open-label (blinded for the two ENERZAIR® BREEZHALER® tested doses), active-controlled study comparing the efficacy and safety of ENERZAIR® BREEZHALER®/ATECTURA® BREEZHALER® with a free combination of salmeterol xinafoate/fluticasone propionate (Sal/Flu) plus tiotropium (Tio) in patients with uncontrolled asthma.

The purpose of this trial was to demonstrate that the efficacy of two doses of the fixed-dose combination product ENERZAIR® BREEZHALER® (150/50/160 μg and 150/50/80 μg) is non-inferior to the efficacy of the free combination of Sal/Flu (50/500 μg) plus Tio (5 μg) in patients with uncontrolled asthma.

Primary endpoint: demonstrate non-inferiority of both doses of ENERZAIR® BREEZHALER® to comparator Sal/Flu plus Tio after 24 weeks of treatment based on the Asthma Quality of Life Questionnaire (AQLQ).

Secondary endpoints (secondary analyses not controlled for multiplicity; inferences based on these data cannot be made due to lack of power):

  • To evaluate efficacy of both doses of ENERZAIR® BREEZHALER® compared with Sal/Flu plus Tio based on trough FEV1 after 24 weeks of treatment.
  • To evaluate efficacy of both doses of ENERZAIR® BREEZHALER® compared with Sal/Flu plus Tio based on Asthma Quality of Life Questionnaire (AQLQ) over 24 weeks of treatment.
  • To evaluate efficacy of both doses of ENERZAIR® BREEZHALER® compared with Sal/Flu plus Tio based on ACQ-7 over 24 weeks of treatment.
  • To evaluate efficacy of both doses of ENERZAIR® BREEZHALER® compared with Sal/Flu plus Tio based on lung function over 24 weeks of treatment.
 

The IRIDIUM* trial showed an improvement in lung function with high-dose ENERZAIR® BREEZHALER® vs high-dose IND/MF.5

ENERZAIR® BREEZHALER® high-dose significantly improved trough FEV1 by +65 mL (95% CI: 31, 99) at Week 26 vs. ATECTURA® BREEZHALER® high-dose, p<0.0015

 

Change from baseline in trough FEV1 in high dose ATECTURA® BREEZHALER® vs high dose ENERZAIR® BREEZHALER® at Week 26 and 525

Week 26

 

Week 525,6

 

LS mean change from baseline in trough FEV1 in high dose SAL/FLU vs high dose ENERZAIR® BREEZHALER® at Weeks 26 and 525,6

 

The ARGON* trial showed an improvement in lung function with high-dose ENERZAIR® BREEZHALER® vs high-dose SAL/FLU.7

 

LS mean change from baseline in trough FEV1 in high dose SAL/FLU vs high dose ENERZAIR® BREEZHALER® at Week 247

 

The IRIDIUM*† trial showed a fast onset of action with high dose of ENERZAIR® BREEZHALER®, with at least 50 mL improvements in FEV1 versus both doses of ATECTURA® BREEZHALER®, and at least 114 mL improvement versus FLU–SAL, observed as early as 5 min on Day 1 and sustained at all timepoints across 52 weeks.5,6

Onset of action: LS mean change from baseline in trough FEV1 in first hour post-dose (measured 5–60 minutes post-dose on Day 1)6

In the IRIDIUM trial* , all treatment groups showed clinically relevant improvements from baseline in ACQ-7 at week 26; however, no statistically significant differences between groups were observed.5

LS mean change in ACQ-7 score from baseline to Week 265

 

 

 

Percentage of responders achieving a minimal clinically important difference (MCID) in ACQ-7 score from Week 4 through to Week 526

 

 

The ARGON* trial showed non-inferiority in AQLQ total score with high-dose ENERZAIR® BREEZHALER® vs high dose SAL/FLU + TIO at Week 24.7

 

Change from baseline in AQLQ total score with ENERZAIR® BREEZHALER® high-dose vs. SAL/FLU high-dose + TIO at Week 247

 

 

AQLQ responders§ with ENERZAIR® BREEZHALER® high-dose vs. SAL/FLU high-dose + TIO at Week 247

 

Severe exacerbations reduction

Exacerbations were a secondary endpoint (not part of confirmatory testing strategy).1

The IRIDIUM* trial showed that high-dose ENERZAIR® BREEZHALER® once daily demonstrated a reduction in the annual rate of exacerbations compared to high doses of SAL/FLU twice daily and ATECTURA® BREEZHALER® once daily.5

Annualised rate of severe exacerbations between high dose ENERZAIR® BREEZHALER® vs high dose ATECTURA® BREEZHALER® and high dose SAL/FLU5

 

ENERZAIR® BREEZHALER® were generally well-tolerated

The ENERZAIR® BREEZHALER® device was well tolerated: AEs and SAEs were balanced and safety was comparable across treatment arms.5,7

 

The PLATINUM trial programme

>7,500 patients

still symptomatic on low-dose ICS up to high-dose LABA/ICS treatment were included5–8

 (ENERZAIR® BREEZHALER®)1,5

  • Very common AEs** during the trial included asthma exacerbation and nasopharyngitis
  • Common AEs†† included upper respiratory tract infection, candidiasis, urinary tract infection, hypersensitivity, headache, tachycardia, oropharyngeal pain, cough, dysphonia, gastroenteritis, musculoskeletal pain, muscle spasms and pyrexia
  • SAEs included asthma exacerbation, pneumonia, lower respiratory tract infection, cholelithiasis and pulmonary embolism

 (ENERZAIR® BREEZHALER®)7

  • Very common AEs** during the trial included asthma exacerbation
  • Common AEs†† (affecting ≥2% in at least one treatment arm) included nasopharyngitis, bronchitis, pharyngitis, upper respiratory tract infection, headache, respiratory tract infection viral and viral upper respiratory tract infection
  • SAEs included asthma exacerbation, pneumonia and atrioventricular block (second degree)

 

Very common AEs affect ≥1/10. Common AEs affect between ≥1/100 to <1/10.

 

*The doses reported within the clinical trials were contained dose rather than the delivered dose.
None of these secondary analyses were controlled for multiplicity;5 inferences based on these data cannot be made due to lack of power.
ACQ-7 responder = patient achieving a minimal clinically important difference (MCID) of ≥0.5-point improvement from baseline in ACQ-7 score.5
A severe exacerbation was defined as an aggravation of asthma symptoms (such as shortness of breath, cough, wheezing, or chest tightness) that requires systemic corticosteroids for at least 3 consecutive days or a need for an emergency room visit, hospitalisation owing to asthma, or death due to asthma.
§AQLQ responder = patient achieving a minimal clinically important difference (MCID) of ≥0.5-point improvement from baseline in AQLQ score.4
**Very common AEs affect ≥1/10.
††Common AEs affect between ≥1/100 to <1/10.

IND/GLY/MF (ENERZAIR® BREEZHALER®) high-dose = IND/GLY/MF 150/50/160 μg (once-daily); IND/MF (ATECTURA® BREEZHALER®) medium-dose = IND/MF 150/160 μg (once-daily); IND/MF (ATECTURA® BREEZHALER®) high-dose = IND/MF 150/320 μg (once-daily); SAL/FLU high-dose = SAL/FLU 50/500 μg (twice-daily).

ACQ-7, Asthma Control Questionnaire-7; AE, adverse event; AQLQ; asthma quality of life questionnaire; CI, confidence interval; FEV1, forced expiratory lung volume; FLU, fluticasone propionate; GINA, Global Initiative for Asthma; GLY, glycopyrronium; ICS, inhaled corticosteroid; IND, indacaterol; LABA, long acting beta agonist; LAMA, long acting muscarinic antagonist; LS, least square; MCID, minimal clinically important difference; MF, mometasone furoate; SAE, serious adverse event; SAL, salmeterol xinafoate; TIO, tiotropium.

References

  1. ENERZAIR® BREEZHALER®. Summary of Product Characteristics. July 2020.
  2. Novartis Press Release. Novartis receives EC approval for Enerzair® Breezhaler®, including the first digital companion (sensor and app) that can be prescribed alongside a treatment for uncontrolled asthma in the EU. Available at: https://www.novartis.com/news/media-releases/novartis-receives-ec-approv.... Date accessed: January 2021.
  3. Novartis Press Release. Novartis announces positive results from Phase III IRIDIUM study of inhaled combination QVM149 in patients with uncontrolled asthma. Available at: https://www.novartis.com/news/media-releases/novartis-announces-positive.... Date accessed: January 2021.
  4. Novartis Press Release. Novartis Phase IIIb ARGON study meets primary endpoint in a comparison of Enerzair® Breezhaler® (QVM149) versus a free combination of two existing inhaled treatments in uncontrolled asthma. Available at: https://www.novartis.com/news/media-releases/novartis-phase-iiib-argon-s.... Date accessed: January 2021.
  5. Kerstjens H, et al. Lancet Respir Med 2020;8(10):1000–1012.
  6. Kerstjens H, et al. Lancet Respir Med 2020 supplementary appendix 1;8(10):1000–1012.
  7. Gessner C, et al. Respir Med 2020;170:106021 [Epub ahead of print].
  8. Kornmann O, et al. Respir Med 2020;161105809 [Epub ahead of print].
UK | February 2021 | 103403
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
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