AstraZeneca announced positive results from the phase 3 ETHOS trial which compared triple-combination therapy Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate) with two dual combination therapies: Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (single inhaler, fixed-dose budesonide and formoterol fumarate), in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Treatment with Breztri Aerosphere resulted in a statistically significant reduction in the rate of moderate or severe exacerbations versus the dual combination treatments, thus reaching the primary endpoint. The results were published in the New England Journal of Medicine and simultaneously presented at the American Thoracic Society virtual Scientific Symposium, Clinical Trial Results in Pulmonary Medicine. AstraZeneca will continue to review these data with health authorities.
The randomized, double-blinded, multi-center, parallel-group, 52-week ETHOS trial enrolled more than 8,500 patients who had experienced ≥1 moderate/severe exacerbation in the previous year and were receiving at least two inhaled maintenance treatments at entry into the trial. Outcomes in the ETHOS trial included, as a primary endpoint, the rate of moderate or severe exacerbations.
Compared with Bevespi Aerosphere, Breztri Aerosphere achieved a 24% reduction in exacerbations. Breztri Aerosphere achieved a 13% reduction compared with PT009. 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.
The safety and tolerability of Breztri Aerosphere were consistent with the known profiles of the dual comparators. In the trial, the most frequently reported adverse events were nasopharyngitis, COPD and upper respiratory tract infection.
Breztri Aerosphere is approved in Japan and China for patients with COPD. It is under regulatory review in the US and EU.
About Breztri Aerosphere
Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate) is a single-inhaler, fixed dose triple-combination of budesonide, an inhaled corticosteroid, with glycopyrronium, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA).
Under the terms of the agreement to acquire Pearl Therapeutics Inc., AstraZeneca anticipates making a $150m milestone payment upon US regulatory approval of Breztri Aerosphere for COPD. This payment would be the final development and regulatory milestone under that agreement.
COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 384 million people and is the third leading cause of death globally. Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important treatment goals in the management of COPD. Even a single COPD exacerbation may be associated with a significant increase in the rate of decline in lung function, a significant deterioration in quality of life, and can significantly reduce life expectancy and increase the risk of mortality.