Trixeo Aerosphere is the third triple combination inhaler to become available for patients with COPD, and the second metered dose inhaler (MDI). Its launch follows the recent introduction of Bevespi Aerosphere, which provides the dual LABA/LAMA combination of formoterol and glycopyrronium via the same Aerosphere MDI.
Trixeo Aerosphere is indicated as a maintenance treatment in adults with moderate to severe COPD who are not adequately treated by the combination of an ICS and a LABA, or a LABA and a LAMA.
The efficacy and safety of formoterol/budesonide/glycopyrronium in patients with moderate to very severe COPD were evaluated in two randomised, double-blind trials.
The 52-week ETHOS trial compared formoterol/budesonide/glycopyrronium MDI (5/160/7.2 microgram) triple therapy with formoterol/glycopyrronium MDI (5/7.2 microgram) and formoterol/budesonide MDI (5/160 microgram) dual therapy, all taken as two inhalations twice daily.
In the modified intention-to treat-population (n=8509), the annual rate of on-treatment moderate or severe COPD exacerbations (primary endpoint) was significantly lower with formoterol/budesonide/glycopyrronium than with formoterol/glycopyrronium (24% lower: rate ratio 0.76; 95% CI 0.69–0.83; p<0.001) or formoterol/budesonide (13% lower: rate ratio 0.87; 95% CI 0.79–0.95; p=0.003).
The 24-week KRONOS trial compared formoterol/budesonide/glycopyrronium MDI (5/160/7.2 microgram) with formoterol/glycopyrronium MDI (5/7.2 microgram), formoterol/budesonide MDI (5/160 microgram), and open-label formoterol/budesonide dry powder inhaler (DPI) 6/200 microgram. A total of 1902 patients were randomised.
The primary endpoints were FEV1 area under the curve from 0–4 hours (FEV1 AUC0–4) over 24 weeks (triple therapy vs formoterol/budesonide MDI and formoterol/budesonide DPI) and change from baseline in morning pre-dose trough FEV1 over 24 weeks (triple therapy vs formoterol/glycopyrronium MDI and non-inferiority for formoterol/budesonide MDI versus formoterol/budesonide DPI).
Over 24 weeks, triple therapy significantly improved FEV1 AUC0-4 compared with formoterol/budesonide MDI (least squares mean difference 104ml, 95% CI 77–131; p<0.0001) and formoterol/budesonide DPI (91ml, 95% CI 64–117; p<0.0001).
Triple therapy also significantly improved pre-dose trough FEV1 versus formoterol/glycopyrronium MDI (22ml, 95% CI 4–39; p=0.0139), and formoterol/budesonide MDI was non-inferior to formoterol/budesonide DPI (-10ml, 95% CI -36 to 16; p=0.4390).
The safety profile of formoterol/budesonide/glycopyrronium triple therapy is characterised by corticosteroid, anticholinergic and ß2-adrenergic class effects related to the individual components of the combination. The most commonly reported adverse reactions are pneumonia (4.6%), headache (2.7%) and urinary tract infection (2.7%).