Phase 3 Trial Updates of QVA149, Glycopyrronium Bromide for COPD

Sosei and Novartis announced further data from their once-daily chronic obstructive pulmonary disease (COPD) clinical trial programs of QVA149 (fixed-dose combination of indacaterol maleate/glycopyrronium bromide) and glycopyrronium bromide.

IGNITE data demonstrated the efficacy of the dual-bronchodilator QVA149 (indacaterol maleate/glycopyrronium bromide) and showed a superior effect on lung function and patient-reported outcomes vs. comparators.

SHINE met its primary endpoint by demonstrating that once-daily QVA149 110/50mcg improved lung function as measured by trough FEV1 compared to once-daily indacaterol maleate 150mcg (+70mL above indacaterol alone; P<0.001) and once-daily glycopyrronium 50mcg (+90mL above glycopyrronium alone; P<0.001). QVA149 was also more effective at improving lung function compared to OL tiotropium 18mcg (+80mL above tiotropium; P<0.001) and placebo (+200mL; P<0.001). Mean peak FEV1 at Week 26 was also significantly higher with QVA149 compared to placebo (+330mL, P<0.001), indacaterol 150mcg (+120mL; P<0.001), glycopyrronium 50mcg (+130mL; P<0.001) and open-label (OL) tiotropium (SpirivaHandiHaler; Boehringer Ingelheim) 18mcg (+130mL; P<0.001). Mean FEV1 area under the curve (AUC) for 0-24hr at Week 26 was significantly higher with QVA149 compared to placebo (+320mL, P<0.001), indacaterol 150mcg (+110mL; P<0.001), glycopyrronium 50mcg (+110mL; P<0.001) and OL tiotropium 18mcg (+110mL; P<0.001).

ILLUMINATE compared QVA149 110/50mcg to twice-daily salmeterol/fluticasone 50/500mcg (Advair Diskus; GlaxoSmithKline) head-to-head over 26 weeks in patients with COPD. The study met its primary endpoint by demonstrating that the mean FEV1 area under the curve (AUC) for 0-12hr at Week 26 was significantly higher with QVA149 compared to salmeterol/fluticasone 50/500mcg (+140mL; P<0.001). Mean FEV1 AUC0-12h was also significantly higher with QVA149 versus salmeterol/fluticasone 50/500mcg at Day 1 (+70mL; P<0.001) and Week 12 (+120mL; P<0.001).

ENLIGHTEN demonstrated the efficacy of QVA149 at improving lung function over a 52-week period by showing that QVA149 increased FEV1 and forced vital capacity (FVC) vs. placebo at Day 1 and Weeks 3, 6, 12, 26, 39 and 52 (P<0.001). At Week 52, the mean difference in FEV1 compared to placebo at 60 minutes post-dose was +257mL (P<0.001).

GLOW pooled analyses demonstrated that investigational glycopyrronium increased lung function, improved patient outcomes compared to placebo. Results of the first pooled analysis of GLOW1 and GLOW2 data demonstrated that patients on glycopyrronium 50mcg experienced rapid, sustained and clinically meaningful bronchodilation over 52 weeks. The improvement in FEV1 was seen within five minutes after the first dose on Day 1 (+90mL at 5 minutes and +144mL at 15 minutes vs. placebo; P<0.001) and was sustained throughout the 52-week period (P<0.001 vs. placebo). FEV1 AUC for 0-4h, 0-12h, 0-24h and 12-24h for glycopyrronium 50mcg was statistically significantly greater than placebo (P<0.05) and numerically greater than OL tiotropium 18mcg (an exploratory arm in GLOW2) when compared to placebo on Day 1 and Weeks 12, 26 and 52. When compared to placebo, glycopyrronium 50 mcg was also numerically higher than OL tiotropium 18mcg vs. placebo at all-time points for trough FEV1 (Day 1 and Weeks 12, 26 and 52).

The second pooled analysis of GLOW1 and GLOW2 data found that for patients taking glycopyrronium 50mcg, the time to first moderate/severe exacerbation was significantly prolonged compared to placebo at both Week 26 (hazard ratio [HR] 0.64; P<0.001) and Week 52 (HR 0.67; p<0.001)[4]. The results were comparable in patients treated with OL tiotropium 18mcg. Glycopyrronium 50mcg also significantly lowered the rate of moderate/severe exacerbations vs. placebo at Weeks 26 and 52 (both rate ratio [RR] 0.66; P<0.005).

Indacaterol maleate is a long-acting beta2-adrenergic agonist (LABA). Glycopyrronium bromide is a long-acting muscarinic antagonist (LAMA).

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