Novartis announces positive results from phase III IRIDIUM study of inhaled combination QVM 149 in patients with uncontrolled asthma

Novartis announced that investigational, once-daily, inhaled QVM 149 (indacaterol acetate, glycopyrronium bromide and mometasone furoate or IND/GLY/MF) was superior to QMF 149 (indacaterol acetate and mometasone furoate or IND/MF) in improving trough forced expiratory volume in one second (FEV1) after 26 weeks, meeting the primary endpoint of the Phase III IRIDIUM clinical trial . This superior improvement in lung function was achieved in asthma patients who were uncontrolled on treatment with a long-acting beta agonist/inhaled corticosteroid (LABA/ICS). IND/GLY/MF was generally well tolerated and safety was comparable across treatment arms

The key secondary endpoint was improvement in Asthma Control Questionnaire (ACQ-7) score for IND/GLY/MF versus IND/MF. Tested treatments delivered clinically meaningful improvements in this measure of symptoms from baseline at Week 26, but the key secondary endpoint was not met. Among other secondary endpoints, IRIDIUM explored reduction of asthma exacerbation rates, where a substantial reduction was observed in moderate-to-severe and severe asthma exacerbation rates with IND/GLY/MF compared with an established LABA/ICS standard of care (twice-daily salmeterol xinafoate/fluticasone propionate 50/500 �g). The IRIDIUM study was conducted to evaluate the efficacy and safety of medium and high doses of IND/GLY/MF (150/50/80 �g and 150/50/160 �g) versus respective medium and high doses of IND/MF (150/160 �g and 150/320 �g) delivered via the dose-confirming Breezhaler device, as well as versus twice-daily salmeterol/fluticasone (50/500 �g) delivered via the Accuhaler. Patients with uncontrolled asthma on medium and high doses of LABA/ICS (as determined by pulmonary function testing and effects on asthma control) were included.

�Despite being on treatment with LABA/ICS, nearly half of all patients with moderate-to-severe asthma are uncontrolled and at a higher risk of exacerbations, hospitalization or even death,� said Dr. Huib Kerstjens, University Medical Center Groningen, The Netherlands. �For these patients, it is important to explore additional options to improve treatment outcomes and quality of life. The initial results of IRIDIUM show us that QVM149 can improve lung function in these patients and potentially deliver substantial reduction in exacerbation rates, which can have a significant impact on the daily lives of people with uncontrolled asthma.�

The overall incidence of adverse events (AEs) and serious AEs in IRIDIUM was comparable among treatment groups and consistent with the known safety profile of the monocomponents.

About the IRIDIUM Clinical Trial : IRIDIUM is a Phase III, multicenter, randomized, double-blind, parallel-group study, designed to compare the efficacy and safety of QVM 149 (IND/GLY/MF) with QMF 149 (IND/MF) in patients with asthma. The purpose of the trial was to evaluate the efficacy and safety of two different doses of IND/GLY/MF (150/50/80 �g and 150/50/160 �g) versus two respective IND/MF doses (150/160 �g and 150/320 �g) in patients with uncontrolled asthma, as determined by pulmonary function testing and effects on asthma control. All patients were required to be symptomatic at screening despite being on treatment with medium or high stable doses of LABA/ICS. Approximately 3092 male and female adult patients with asthma were randomized 1:1:1:1:1 (approximately 618 patients in each of the treatment groups) to receive either:IND/GLY/MF 150/50/80 �g (once daily).IND/GLY/MF 150/50/160 �g (once daily).IND/MF 150/160 �g (once daily). IND/MF 150/320 �g (once daily).Salmeterol xinafoate/fluticasone propionate (SFC) 50/500 �g (twice daily, via Accuhaler) The primary objective of this study was to demonstrate superiority of either IND/GLY/MF 150/50/80 �g versus IND/MF 150/160 �g or IND/GLY/MF 150/50/160 �g versus IND/MF 150/320 �g, all delivered once daily, in improving trough FEV1 (volume of air that can be forced out in the first second of expiration approximately 24 hours post administration of study drug) after 26 weeks of treatment in patients with asthma.

The key secondary objective was to demonstrate the superiority of either IND/GLY/MF 150/50/80 �g versus IND/MF 150/160 �g or IND/GLY/MF 150/50/160 �g versus IND/MF 150/320 �g, in improving ACQ-7 score after 26 weeks of treatment in patients with asthma. Other secondary endpoints also included reduction of exacerbation rate, comparing IND/GLY/MF 150/50/80 �g with IND/MF 150/160 �g and IND/GLY/MF 150/50/160 �g with IND/MF 150/320 �g. Exacerbation rate was also measured for both doses of IND/GLY/MF compared with SFC (50/500 �g).