Novartis Announces Phase III IRIDIUM Trial Results Showing Enerzair Breezhaler Superior to Advair in Lung Function and Exacerbation Reduction for Uncontrolled Asthma

July 13, 2020 /Bioon/ -- Novartis recently announced that the full results of the Phase III IRIDIUM study (NCT02571777) on Enerzair Breezhaler (QVM149; indacaterol acetate/glycopyrronium bromide/mometasone furoate; IND/GLY/MF), a novel triple-combination therapy for asthma, have been published in The Lancet Respiratory Medicine.

The results showed that treatment with Enerzair Breezhaler achieved a statistically significant improvement in lung function compared with Atectura Breezhaler (QMF149, IND/MF, indacaterol acetate/mometasone furoate). The key secondary endpoint was the comparison of improvements in Asthma Control Questionnaire (ACQ-7) scores between Enerzair Breezhaler and Atectura Breezhaler; although both therapies produced clinically meaningful improvements in this regard, the key secondary endpoint was not met. In other secondary endpoint analyses, compared with an established LABA/ICS standard of care (salmeterol/fluticasone propionate [Advair, Seretide, high-dose Sal/Flu (50/500 μg)], twice daily), Enerzair Breezhaler improved lung function and significantly reduced the rate of moderate-to-severe and severe asthma exacerbations.

It is worth noting that Enerzair Breezhaler is the first once-daily fixed-dose combination product of LABA/LAMA/ICS approved in Europe, and also the first asthma treatment regimen in the European Union that can be prescribed with a digital companion (the Propeller Health sensor and application customized for the Breezhaler device). This digital companion provides patients with inhalation confirmation, medication reminders, and access to objective treatment data, which can be shared with physicians to help them make better treatment decisions.

Currently, once-daily Enerzair Breezhaler (IND/GLY/MF) has been approved in Japan, Canada, and the European Union. Once-daily Atectura Breezhaler (IND/MF), a fixed-dose combination of a long-acting beta2-agonist (LABA) and an inhaled corticosteroid (ICS), has also been approved in the European Union, Japan, and Canada. It is indicated as maintenance therapy for adult and adolescent patients aged ≥12 years with asthma whose disease is not adequately controlled with inhaled corticosteroids (ICS) and short-acting beta2-agonists (SABA).

Novartis is committed to making Enerzair Breezhaler (IND/GLY/MF) and Atectura Breezhaler (IND/MF) available to patients worldwide. These two products are currently undergoing regulatory review in multiple countries, including Switzerland. As part of Novartis’s ongoing commitment to reducing the environmental impact of its asthma portfolio, both products will be administered via the Breezhaler® device, which does not use hydrofluoroalkanes/chlorofluorocarbons (HFA/CFC).

Professor Huib Kerstjens, Head of the Department of Pulmonary Diseases at the University Medical Center Groningen, stated: “Data from the IRIDIUM study demonstrate that once-daily IND/GLY/MF improved lung function and reduced exacerbations in patients who remained symptomatic despite receiving standard-of-care LABA/ICS therapy. These findings are encouraging, as achieving optimal symptom control in asthma remains challenging; at least 45% of patients in GINA Steps 4 and 5 remain uncontrolled, which can lead to diminished quality of life, reduced work productivity, and increased use of emergency or hospital-based healthcare services.”

Dominic Brittain, Global Program Head for Respiratory at Novartis Pharmaceuticals, stated: “At Novartis, we are committed to reimagining respiratory care by delivering innovative medicines and digital solutions to patients. Given the relatively limited advancements in inhaled asthma therapies over the past decade, the potential of IND/GLY/MF as a once-daily, fixed-dose combination therapy for uncontrolled asthma is highly exciting, as demonstrated in this pivotal study.”

The IRIDIUM study is a randomized, double-blind, parallel-group, multicenter Phase III trial conducted in over 3,000 patients with asthma, designed to compare the efficacy and safety of IND/GLY/MF versus IND/MF for the treatment of asthma. The objective of this study was to evaluate two different doses of IND/GLY/MF (high dose: 150/50/160 μg; medium dose: 150/50/80 μg) against two corresponding doses of IND/MF (high dose: 150/320 μg; medium dose: 150/160 μg).

All patients enrolled in the study, despite receiving stable medium- or high-dose LABA/ICS therapy, had asthma symptoms at screening and experienced one or more exacerbations in the previous year. In the study, approximately 3,092 adult male and female patients with asthma were randomized in a 1:1:1:1:1 ratio (approximately 618 patients per group) to receive the following treatment regimens: (1) IND/GLY/MF 150/50/80 μg (once daily)；（2）IND/GLY/MF 150/50/160 μg (once daily); (3) IND/MF 150/160 μg (once daily);(4) IND/MF 150/320 μg (once daily); (5)Sal/Flu 50/500 μg (twice daily).

The primary endpoint of the study was the superiority of high-dose IND/GLY/MF over high-dose IND/MF, and of medium-dose IND/GLY/MF over medium-dose IND/MF, in improving FEV1 (forced expiratory volume in 1 second measured 24 hours post-dose) in patients with asthma after 26 weeks of treatment. The key secondary endpoint was the superiority of the two doses of IND/GLY/MF over the corresponding two doses of IND/MF in improving Asthma Control Questionnaire-7 (ACQ-7) scores after 26 weeks of treatment. Secondary endpoints included reductions in exacerbation rates, comparing the two doses of IND/GLY/MF with the corresponding two doses of IND/MF, and comparing the two doses of IND/GLY/MF with salmeterol/fluticasone propionate (Sal/Flu; 50/500 μg).

The results showed that the study met its primary endpoint: at Week 26 of treatment, high-dose and medium-dose IND/GLY/MF demonstrated statistically significant improvements in trough forced expiratory volume in one second (trough FEV1) compared with the corresponding two doses of IND/MF (0.065 L, p < 0.001; 0.076 L, p < 0.001, respectively). Regarding key secondary endpoints, both treatments achieved clinically meaningful improvements from baseline in ACQ-7 scores at Week 26, but the key secondary endpoints were not met.

Secondary endpoint analysis showed that at Week 26 of treatment, both doses of IND/GLY/MF resulted in significant improvements in lung function (FEV1) compared with high-dose Sal/Flu (high dose [0.119 L; p<0.001]; medium dose [0.099 L; p<0.001]). Similar FEV1 improvements were observed across all comparisons at Week 52, indicating the potential long-term benefits of IND/GLY/MF as a maintenance therapy. Compared with corresponding doses of IND/MF and high-dose Sal/Flu (p<0.001), improvements in FEV1 were observed as early as 5 minutes after the first dose, demonstrating the rapid onset of action of IND/GLY/MF.

In further secondary endpoint analyses, high-dose IND/GLY/MF significantly reduced the rates of moderate-to-severe (36%; p<0.001) and severe (42%; p<0.001) asthma exacerbations compared with high-dose Sal/Flu. Compared with high-dose Sal/Flu1, medium-dose IND/GLY/MF also demonstrated reductions in the rates of moderate-to-severe (19%; p=0.041) and severe (16%; p=0.117) asthma exacerbations.

In the study, the overall incidence of adverse events (AEs) and serious adverse events (SAEs) with IND/GLY/MF and IND/MF was generally low and comparable across treatment groups. Asthma exacerbation was the most common AE and SAE. (Bioon.com)