Novartis Highlights High-Dose Enerzair Breezhaler’s Significant Reduction in Moderate-to-Severe Asthma Exacerbations in Prospectus Filing

Compiled by Fan Dongdong

Recently, Novartis announced that in patients with asthma uncontrolled by medium- or high-dose long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) therapy, once-daily high-dose Enerzair Breezhaler combination (indacaterol acetate/glycopyrronium bromide/mometasone furoate, IND/GLY/MF) significantly reduced the rate of moderate or severe asthma exacerbations compared to once-daily medium-dose therapy.

IRIDIUM is a Phase III, multicenter, randomized, double-blind, parallel-group study designed to compare the efficacy and safety of IND/GLY/MF versus IND/MF in patients with asthma. The objective of this study is to evaluate the efficacy of two different doses of IND/GLY/MF (high dose: 150/50/160 μg; medium dose: 150/50/80 μg) relative to two corresponding doses of IND/MF (high dose: 150/320 μg; medium dose: 150/160 μg) in patients with uncontrolled asthma. Patients enrolled in the trial were symptomatic at screening and had experienced exacerbations in the previous year.

Approximately 3,092 patients with asthma participated in this trial. Patients were randomly assigned in a 1:1:1:1:1 ratio to one of the following treatment groups (approximately 618 patients per group): IND/GLY/MF 150/50/80 μg (once daily), IND/GLY/MF 150/50/160 μg (once daily), IND/MF 150/160 μg (once daily), IND/MF 150/320 μg (once daily), or Sal/Flu 50/500 μg (twice daily).

The primary objective of this study was to demonstrate the efficacy of high-dose IND/GLY/MF versus high-dose IND/MF, and medium-dose IND/GLY/MF versus medium-dose IND/MF, in improving trough FEV1 after 26 weeks of treatment in patients with asthma. The key secondary endpoint was to demonstrate the superiority of both doses of IND/GLY/MF over both doses of IND/MF in improving Asthma Control Questionnaire (ACQ) scores after 26 weeks of treatment in patients with asthma. Other secondary endpoints included the reduction in exacerbation rates with high-dose IND/GLY/MF compared with high-dose IND/MF, and with medium-dose IND/GLY/MF compared with medium-dose IND/MF. Secondary analyses also included comparisons of the efficacy of both doses of IND/GLY/MF with salmeterol/fluticasone propionate (Sal/Flu; 50/500 μg).

Analysis showed that, compared with moderate-dose (150/50/80 μg) therapy over 52 weeks, high-dose triple therapy reduced the annualized rate of moderate or severe asthma exacerbations by 21% (p = 0.026). This therapy also reduced the annualized rate of severe acute asthma exacerbations in patients whose condition was not adequately controlled with current inhalation therapy by 31% (p = 0.003). Compared with the moderate dose, high-dose triple therapy further reduced the annualized rate of all exacerbations (mild, moderate, and severe) by 14% (p = 0.132), although this finding was not statistically significant. Both tested doses demonstrated favorable safety and tolerability profiles.

Post-hoc analysis of the pivotal Phase III IRIDIUM study demonstrated that the safety profile of high-dose triple therapy was consistent with findings from the prior Phase III/IIIb PLATINUM clinical development program. This post-hoc analysis supports the potential of high-dose IND/GLY/MF as an effective step-up treatment option to further reduce exacerbations in patients with uncontrolled asthma. The findings also complement the efficacy and safety data from the pivotal IRIDIUM study, which indicated that high-dose triple therapy has the potential to improve lung function and reduce exacerbations compared with salmeterol/fluticasone (Sal/Flu).

Novartis’ Enerzair Breezhaler triple therapy is a fixed-dose combination product comprising indacaterol acetate (a long-acting beta2-agonist, LABA), glycopyrronium bromide (GLY, a long-acting muscarinic antagonist, LAMA), and mometasone furoate (MF, a high-dose inhaled corticosteroid, ICS). Enerzair Breezhaler is administered via the Breezhaler device, which features a dose confirmation mechanism and enables once-daily inhalation therapy using a single inhaler. This therapy received European Union approval in July this year.

Reference source: Novartis post hoc analysis shows high-dose Enerzair Breezhaler reduces asthma exacerbations versus medium-dose, complementing key pivotal IRIDIUM study findings