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.

Novartis announced that full results from the Phase IIIb ARGON study were published online in Respiratory Medicine .. These results show that once-daily treatment with single inhaler, high- and medium-dose Enerzair Breezhaler (QVM149; indacaterol acetate, glycopyrronium bromide and mometasone furoate [IND/GLY/MF]) demonstrated non-inferiority to a free combination of twice-daily, high-dose salmeterol xinafoate/fluticasone propionate (Sal/Flu) plus once-daily tiotropium (Tio), delivered in two different devices, in improving quality of life in people with uncontrolled asthma.

Among secondary analyses, improvements in lung function, asthma control, health status, and reductions in moderate exacerbations were observed with high-dose once-daily IND/GLY/MF compared to high-dose Sal/Flu plus Tio1.

“Today, over 45% of patients at GINA Steps 4 and 5 remain uncontrolled, despite current therapy, demonstrating the need for additional treatment options in this patient population,” said Assistant Professor Christian Gessner, Head of POIS Leipzig Study Centre and Guest Doctor at Universität Leipzig. “The ARGON study shows that once-daily IND/GLY/MF improves quality of life and, if approved, could provide an effective and convenient treatment for patients whose asthma is uncontrolled with LABA/ICS treatment.”

The primary endpoint of the study was met, with both high- and medium- doses of IND/GLY/MF demonstrating non-inferiority in change from baseline in Asthma Quality of Life Questionnaire (AQLQ) score (high: 0.073; medium: ?0.038; both p<0.001).

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In secondary analyses , improvements in asthma control (as measured by Asthma Control Questionnaire; ACQ-7 score [-0.124; p=0.004]) and lung function (as measured by trough FEV1 [96 mL; p<0.001]) were seen with high-dose IND/GLY/MF compared with high-dose Sal/Flu plus Tio1. In additional exploratory analyses, improvements in health status (as measured by St. George’s Respiratory Questionnaire; SGRQ [-2.00; p=0.04]), and peak expiratory flow (morning [9.56 L/min; p=0.005], evening [9.15 L/min; p=0.006]) were seen with high-dose IND/GLY/MF compared with high-dose Sal/Flu plus Tio1. A greater reduction in the rate of moderate exacerbations (43%; p=0.04) was seen with high-dose IND/GLY/MF versus high-dose Sal/Flu plus Tio; the rate of exacerbations across all severities was comparable between the two treatment groups. Comparable efficacy in these endpoints was seen with medium-dose IND/GLY/MF versus high-dose Sal/Flu plus Tio, but at a corresponding lower steroid dose. Adverse events were generally comparable across treatments.

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The ARGON study assessed IND/GLY/MF, a once-daily, fixed-dose combination of a long-acting beta2-agonist (LABA), a long-acting muscarinic antagonist (LAMA) and an inhaled corticosteroid (ICS) in high- (150/50/160 µg) and medium- (150/50/80 µg) doses, delivered via the Breezhaler, compared with a free combination of twice-daily high-dose Sal/Flu (50/500 µg) plus once-daily Tio (5 µg) in patients with asthma not adequately controlled on current inhaled therapies, over 24 weeks of active treatment.

To date, high-dose IND/GLY/MF has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP); this submission was supported by the IRIDIUM study. The positive opinion for Enerzair Breezhaler also covered a digital companion with app and sensor that provide inhalation confirmation, medication reminders and access to objective data to better support therapeutic decisions. Further regulatory reviews are currently underway in multiple countries, including Switzerland and Japan.

See-

Gessner C et al. “Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON)”. Resp Med 2020;106021. DOI: https://doi.org/10.1016/j.rmed.2020.106021.