FDA Approves Triple Fixed-dose Inhaled Therapy for COPD

July 24, 2020

Approval was awarded to AstraZeneca for an inhaled, fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate.

The US Food and Drug Administration (FDA) approved on July 23, 2020, budesonide/glycopyrrolate/formoterol fumarate (Breztri Aerosphere, AstraZeneca), a triple fixed-dose maintenance therapy for patients with chronic obstructive pulmonary disease (COPD).

The approval, announced in a press release today by manufacturer AstraZeneca, is based on positive results from the phase 3 ETHOS trial where the triple combination treatment resulted in a statistically significant reduction in the rate of moderate or severe COPD exacerbations compared with dual-combination therapies glycopyrrolate/formoterol fumarate and PT009 (budesonide/formoterol fumarate). The ETHOS study was published in June in the New England Journal of Medicine.

Safety and efficacy data for budesonide/glycopyrrolate/formoterol fumarate from the phase 3 KRONOS trial also were considered in the FDA approval. In both trials, the safety and tolerability of the triple therapy were consistent with the profiles of the dual comparators.

The 52-week randomized ETHOS trial evaluated the efficacy and safety of triple therapy at 2 dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least 1 exacerbation in the past year.

Patients were assignedin a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [budesonide 320 μg or 160 μg), a LAMA [glycopyrrolate 18 μg], and a LABA [formoterol 9.6 μg]) or one of two dual therapies ( glycopyrrolate 18 μg/fomoterol 9.6 μg or budesonide 320 μg/formoterol 9.6 μg )

Among the 8509 patients in the intention-to-treat population, annual rates of moderate or severe exacerbations in the triple therapy groups were 1.08 (budesonide 320 μg) and 1.07 (budesonide 160 μg). Rates in the dual combination therapy groups were 1.42 (glycopyrrolate–formoterol) and 1.24 (budesonide–formoterol).

Adverse events were similar across treatment groups.

“Preventing exacerbations is central to the management of chronic obstructive pulmonary disease," said Dr. Fernando J. Martinez, Chief of Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine and New York-Presbyterian Weill Cornell Medical Center, New York, US and Investigator in the ETHOS trial in the press release.

"Even a single exacerbation can have a negative impact on a patient’s lung function and quality of life, and it can increase the risk of death."

The triple combination is not indicated for the relief of acute bronchospasm or for the treatment of asthma.