FDA Approves Breztri Aerosphere for Asthma; EU CHMP Recommends Trixeo

Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate), AstraZeneca's single-inhaler triple therapy, was approved by the U.S. FDA as a maintenance treatment for asthma in patients aged at least 12 years, and the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended approval of the same therapy, branded Trixeo Aerosphere in Europe, for asthma maintenance in people aged above 12. Both regulatory actions are based on data from the Phase III KALOS and LOGOS trials.

The inhaler combines 320 μg budesonide (an inhaled corticosteroid), 36 μg glycopyrrolate (a long-acting muscarinic antagonist) and 9.6 μg formoterol fumarate (a long-acting beta2-agonist). It was already approved for maintenance treatment of COPD in the U.S.

KALOS and LOGOS were twin, randomized, double-blind, double-dummy, parallel-group, Phase III trials in adults and adolescents with inadequately controlled asthma. The pooled efficacy set included 4,304 patients. In the pooled analysis, Breztri Aerosphere with 28.8 μg glycopyrrolate was favored over combined dual-therapy comparators for change from baseline in morning pre-dose trough FEV1 over 24 weeks (least-squares mean difference: 76 mL; 95% CI, 57-94; P < .0001) and for FEV1 area under the curve 0–3 hours at week 24 (least-squares mean difference: 90 mL; 95% CI, 72-108; P < .0001). The therapy also reduced the annualized rate of severe asthma exacerbations compared with the combined dual-therapy group (incidence rate ratio: 0.86; 95% CI, 0.76-0.97) and compared with Symbicort alone (IRR: 0.82; 95% CI, 0.71-0.94). Trixeo also demonstrated rapid onset of action, with significant improvement from baseline within five minutes after the first dose.

Adverse event rates were comparable across treatment groups (Breztri with 28.8 μg glycopyrrolate, 53.2%; Breztri with 14.4 μg glycopyrrolate, 60%; Aerosphere comparator, 55.2%; Symbicort, 58.4%). There were no treatment-related deaths, and no new safety signals were identified.

Asthma affects approximately 262 million people globally, including 25 million in the U.S. The primary investigator noted that the trials showed the triple therapy improved lung function and prevented future severe exacerbations regardless of exacerbation history. An AstraZeneca executive said the positive CHMP recommendation, building on the recent FDA approval, underscores the potential of the fixed-dose triple combination to improve outcomes for patients with uncontrolled disease.