The Food and Drug Administration (FDA) has approved Breztri Aerosphere (budesonide/glycopyrrolate/formoterol fumarate; AstraZeneca) for the maintenance treatment of chronic obstructive pulmonary disease (COPD).

In October 2019, the FDA issued a Complete Response Letter (CRL) to AstraZeneca stating that at the time of regulatory submission, the phase 3 ETHOS trial had not been completed and not included in the NDA. Breztri Aerosphere is a single inhaler, fixed-dose triple combination therapy of budesonide, an inhaled corticosteroid with glycopyrrolate, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-agonist (LABA).  

The approval was based on data from the multicenter, double-blind, phase 3 ETHOS trial that compared the efficacy and safety of Breztri Aerosphere to Bevespi Aerosphere (glycopyrrolate/formoterol fumarate) and PT009 (budesonide/formoterol fumarate) in 8588 adult patients with moderate to severe COPD. Patients were randomized 1:1:1:1 to receive twice-daily inhaled doses of Breztri Aerosphere 320/14.4/9.6mcg or 160/14.4/9.6mcg, Bevespi Aerosphere 18/9.6mcg or PT009 320/9.6mcg. The primary end point was the rate of moderate to severe COPD exacerbations.

Results showed that treatment with Breztri Aerosphere 320/14.4/9.6mcg demonstrated a statistically significant reduction in the rate of moderate or severe COPD exacerbations compared with Bevespi Aerosphere (24% lower: rate ratio, 0.76; 95% CI, 0.69-0.83; P <.001) and PT009 (13% lower: rate ratio, 0.87; 95% CI, 0.79-0.95; P =.0027). Moreover, Breztri Aerosphere demonstrated an increase in on-treatment FEV1 AUC0-4 and trough FEV1 at week 24 compared with Bevespi Aerosphere and PT009. 

Additionally, the approval of Breztri Aerosphere is supported by efficacy and safety data from the phase 3 KRONOS trial which showed statistically significant reductions in the rate of moderate or severe COPD exacerbations, along with an increase FEV1 AUC0-4 and trough FEV1 at week 24.

As for safety, the most common adverse reactions (≥2%) are upper respiratory tract infection, pneumonia, back pain, oral candidiasis, influenza, muscle spasm, urinary tract infection, cough, sinusitis and diarrhea.

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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, said: “Preventing exacerbations is central to the management of chronic obstructive pulmonary disease. 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. Breztri Aerosphere has demonstrated significant benefits in reducing exacerbations in patients suffering from COPD.”

The product will be supplied as a pressurized metered-dose inhaler containing 160mcg of budesonide, 9.0mcg of glycopyrrolate, and 4.8mcg of formoterol fumarate per inhalation in 28- and 120-inhalation canisters.

For more information visit breztri.com.