Harnessing the simplicity of the Enerzair Breezhaler for people with severe asthma

By delivering a once-daily three-drug combination therapy in a single device, the Enerzair Breezhaler (indacaterol, glycopyrronium bromide and mometasone furoate) offers a simplified maintenance combination therapy of long-acting beta2-agonist (LABA), long-acting muscarinic agonist (LAMA), and inhaled corticosteroid (ICS) for people with asthma not adequately controlled on a maintenance LABA-ICS combination.1 The limbic spoke to Professor Christine Jenkins about the potential benefits of the Enerzair Breezhaler and its place in asthma therapy.

Despite the simplicity of the Enerzair Breezhaler, Professor Jenkins noted that LABA-LAMA-ICS combination therapy should be reserved for people with severe asthma, in line with the Australian Asthma Handbook (AAH)2 and Global Initiative for Asthma (GINA) recommendations.3 She also emphasised the difference between poor asthma control and severe asthma. “Most respiratory physicians are across this issue, but I do think that the high prevalence of poor asthma control in the community is often confused with severe asthma,” she said. “When we talk about a three-drug combination inhaler therapy that includes a LAMA, these are therapies that despite their simplicity should not be used for the majority of patients. The majority of patients have poorly controlled but not severe asthma,” she explained.

Addressing management issues before diagnosing severe asthma

The prevalence of poorly controlled asthma in Australia is over 50%.4 In contrast, severe asthma – defined as asthma that remains uncontrolled despite high-dose ICS plus LABA therapy – occurs in less than 5% of people with asthma.5 “Severe asthma is a diagnosis you reach at the end of a series of steps that look at the reasons for poor control, recognising those reasons are primarily around adherence and device use and background or ongoing triggers.  And then when you have addressed all of those areas, it’s important to determine the amount of ongoing treatment the person needs to control symptoms, optimise lung function and prevent exacerbations. Only around 5% of people will end up needing more than an ICS-LABA combination,” said Professor Jenkins.

“Every guideline tells us that you don’t declare a person has severe asthma until you have addressed all of the issues that may be contributing to poor asthma control and ascertained that, once they’re addressed, the person still needs a very significant amount of medication to control their symptoms. The issues to consider are the key fundamentals: adherence, device use, background triggers, and ongoing insults that may be aggravating their asthma including cigarette smoking and allergens,” said Professor Jenkins.

Recommendations for managing severe asthma

“If you’ve determined that someone is not controlled on [medium or high-dose] ICS-LABA combination maintenance therapy, then it’s important to consider next steps,” said Professor Jenkins. According to the AAH, people with asthma symptoms on medium to high-dose regular daily ICS-LABA therapy are at Step 4 of treatment.2 In the GINA recommendations, people on medium-dose ICS-LABA are at Step 4 and people on high-dose ICS-LABA are at Step 5.3

If asthma remains inadequately controlled despite correct inhaler technique and adequate adherence, there may be room to increase the ICS dose a little more, explained Professor Jenkins. “We know that there is a not a lot of gain from increasing the ICS too much, and you need to avoid adverse effects as much as possible, particularly since this is a lifelong illness,” she notes.

Another option is to add on treatments such as a LAMA (e.g. tiotropium) to the regular maintenance therapy.2,3 It’s recommended that doses continue to be monitored and adjusted to maintain good symptom control and minimise risks at the lowest effective ICS dose.2,3 “In many parts of Australia where access to respiratory specialists is poor, primary care physicians may naturally consider stepping people with severe asthma onto a three-drug combination that is affordable and easily implemented,” said Professor Jenkins.

For those whose asthma remains uncontrolled, phenotyping is useful in determining whether the asthma is eosinophilic to identify people who might be suitable for biologic therapy, said Professor Jenkins. “If targeted therapies are given to the right person they have impactful effects, particularly reducing exacerbations,” she said.

Delivering once-daily maintenance therapy with the Enerzair Breezhaler

The Enerzair Breezhaler delivers a once daily LABA-LAMA-ICS combination of indacaterol, glycopyrronium bromide and mometasone furoate and is indicated for maintenance treatment of asthma and to reduce exacerbations in adults with asthma not adequately controlled with a maintenance combination of a LABA and an ICS.1

Studies have shown that the once daily three-drug combination (IND-GLY-MF) results in lung function benefits over once daily IND-MF6, twice daily salmeterol-fluticasone (SAL-FLU)6 and loose combination SAL-FLU + tiotropium (TIO).7   

One study6 compared the efficacy and safety of medium- and high-dose IND-GLY-MF delivered via the Enerzair Breezhaler to corresponding doses of IND-MF and also to high-dose (500 µg-50 µg) twice-daily fluticasone propionate (FP) plus salmeterol xinafoate (SALM) delivered via the Diskus device. The study population included people with symptomatic asthma despite treatment with medium- or high-dose ICS-LABA.6 The results showed that the three-drug combination delivered via the Enerzair Breezhaler improved trough FEV1 versus corresponding doses of IND-MF. Improvements in trough FEV1 were also greater for both the medium- and high-dose once daily Enerzair Breezhaler than for high-dose twice daily FP-SALM (500 µg-50 µg) delivered via the Diskus device.6 Overall, the incidence of adverse events as balanced across the treatment groups.6

In a separate study,7 the Enerzair Breezhaler was compared to a combination of twice-daily FP-SALM plus once-daily tiotropium (TIO), which were delivered via separate inhalers. Patients symptomatic despite treatment with medium- or high-dose ICS-LABA were randomised to receive either high-dose (150-50-160 µg) or medium-dose (150-50-80 µg) IND-GLY-MF once daily via the Enerzair Breezhaler, or the free combination of inhalers delivering high-dose twice daily SAL-FLU (50-500 µg) plus once daily TIO (5 µg).

Enerzair Breezhaler was shown to be non-inferior to the free combination inhalers in terms of the Asthma Quality of Life Questionnaire. The high-dose Enerzair Breezhaler was also shown to improve lung function, asthma control and health status compared to the free combination inhalers.

Simplicity of the Enerzair Breezhaler

Professor Jenkins noted the benefit of the Enerzair Breezhaler in simplifying therapy for those requiring a LABA-LAMA-ICS combination. “It’s one device: learn one device and use one device correctly, and the GP and specialist can check that the person is using the device correctly,” she said. “It’s a logical therapy, and it’s effective in treating a number of aspects of moderate to severe asthma, including lung function and symptoms, with a low risk of adverse events. So as a long-term strategy in severe asthma, it’s a very appealing approach,” she said.

For patients requiring a regular daily ICS-LABA combination, the Atectura Breezhaler (indacaterol/mometasone furoate) is available. The Atectura Breezhaler is indicated as a once-daily maintenance treatment in adults and adolescents 12 years of age and older where use of a combination of LABA-ICS is appropriate.7



  1. Enerzair Breezhaler Australian Approved Product Information
  2. National Asthma Council Australia. Australian Asthma Handbook, Version 2.1. National Asthma Council Australia, Melbourne, 2020.
  3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2020.
  4. Reddell H et al. Asthma control in Australia: a cross-sectional web-based survey in a nationally representative population. MJA 2015;202(9):492-498
  5. Hekking PP et al. The prevalence of severe refractory asthma. 2015;135(4):896-902
  6. Kerstjens H et al. Once-daily, single-inhaler mometasone-indacaterol-glycopyrronium versus mometasone-indacaterol or twice-daily fluticasone-salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study. Lancet Respir 2020; 8(10): 1000–10012
  7. Gessner C et al. Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus triptropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Respir Med 2020; 170: 106021
  8. Atectura Breezhaler Australian Approved Product Information

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