General Information

Breztri Aerosphere is a combination of budesonide, an inhaled corticosteroid (ICS); glycopyrrolate, an anticholinergic; and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA).

Breztri Aerosphere is specifically indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease.

Breztri Aerosphere is supplied as an aerosol for oral inhalation. The recommended dosage of Breztri Aerosphere is budesonide 320 mcg, glycopyrrolate 18 mcg and formoterol fumarate 9.6 mcg (administered as 2 inhalations of Breztri Aerosphere [budesonide/glycopyrrolate/formoterol fumarate 160 mcg/9 mcg/4.8 mcg]) twice daily in the morning and in the evening by oral inhalation. Do not take more than two inhalations twice daily. After inhalation, rinse mouth with water without swallowing.

Mechanism of Action

Breztri Aerosphere is a combination of budesonide, glycopyrrolate, and formoterol fumarate. The mechanism of action for the individual components are described below:

Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. Inflammation is an important component in the pathogenesis of COPD. Corticosteroids have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy.

Glycopyrrolate is a long-acting antimuscarinic agent which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation.

Formoterol fumarate is a long-acting selective beta2-adrenergic agonist (beta2-agonist) with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol fumarate, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion 19 Reference ID: 4645600 of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Clinical Trial Results

The FDA approval of Breztri Aerosphere was based on the phase III ETHOS trial, a randomized, double-blinded, multi-center, parallel-group, 52-week trial to assess the efficacy and safety of Breztri Aerosphere in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. The primary endpoint was the rate of moderate or severe exacerbations. Breztri Aerosphere was compared to Bevespi Aerosphere (glycopyrrolate/formoterol fumarate) and PT009 (budesonide/formoterol fumarate). Compared with Bevespi Aerosphere (glycopyrronium/formoterol fumarate), Breztri Aerosphere achieved a 24% reduction in exacerbations. Breztri Aerosphere achieved a 13% reduction (p=0.003) compared with PT009 (budesonide/formoterol fumarate). The dual-combination therapies used as comparators in the trial represent recommended therapeutic classes for the treatment of COPD. In a key secondary endpoint, Breztri Aerosphere showed a 46% reduction in the risk of all-cause mortality compared with Bevespi Aerosphere.