Breztri Aerosphere, AstraZeneca’s triple combination therapy for chronic obstructive pulmonary disease (COPD), significantly reduces the frequency of moderate or severe exacerbations, compared to dual combination therapies, in patients with moderate to very severe forms of the disease, a Phase 3 trial shows.
The findings were presented by the company at the American Thoracic Society virtual Scientific Symposium and published in The New England Journal of Medicine, in an article titled “Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD.”
Breztri Aerosphere, known as PT010 outside of China, is a triple combination therapy made up of the inhalable corticosteroid budesonide, and two types of bronchodilators — the long-acting muscarinic antagonist glycopyrronium and the long-acting β2-agonist formoterol fumarate.
The triple combination therapy is designed to alleviate the symptoms and reduce the frequency of COPD exacerbations — episodes in which disease symptoms suddenly worsen.
The recently-completed Phase 3 ETHOS trial (NCT02465567) assessed the safety and efficacy of Breztri Aerosphere compared to two dual combination therapies also developed by AstraZeneca — Bevespi Aerosphere (glycopyrronium/formoterol fumarate; PT003) and Symbicort (budesonide/formoterol fumarate; PT009) — in patients with moderate-to-severe COPD.
All patients enrolled in the ETHOS trial — more than 8,500 participants — experienced at least one moderate-to-severe exacerbation in the previous year, and received at least two inhaled maintenance treatments before the trial began.
Participants were assigned to receive one of two doses of Breztri Aerosphere (containing 160 or 320 micrograms of budesonide), Bevespi Aerosphere, or Symbicort, for a period of 52 weeks (approximately one year).
The trial’s main goal was to assess the effects of treatment on the rate of moderate-to-severe exacerbations over the course of the study.
Earlier findings from ETHOS showed that both doses of Breztri Aerosphere effectively reduced the frequency of COPD exacerbations, compared to Bevespi Aerosphere or Symbicort.
Full data from the study now announced by the company showed that when given at the highest dose, Breztri Aerosphere reduced the frequency of exacerbations by 24% compared to Bevespi Aerosphere, and by 13% compared to Symbicort.
Similar results were seen with the lowest dose of the triple combination therapy (containing 160 micrograms of budesonide), which lowered the rate of COPD exacerbations by 25% compared to Bevespi Aerosphere, and by 14% compared to Symbicort.
A key secondary goal of the study also showed that Breztri Aerosphere reduced the risk of death by 46% compared to Bevespi Aerosphere.
“The Phase 3 ETHOS trial results are important and demonstrate the benefit of Breztri Aerosphere in reducing the rate of exacerbations in this progressive disease,” Klaus Rabe, MD, PhD, professor of pulmonary medicine at the University of Kiel, director of the department of pneumology at Clinic Grosshansdorf, both in Germany, and lead investigator of ETHOS, said in a press release.
“The findings also show that reducing risk of all-cause mortality is achievable and could transform treatment goals in chronic obstructive pulmonary disease,” he added.
The safety profile of the triple combination therapy was consistent with that of the dual combination therapies used as reference treatments during ETHOS.
The incidence of adverse events was similar in all treatment groups, ranging from 61.7% to 64.5%. The most common adverse events observed during the study included nasopharyngitis (common cold) and upper respiratory tract infections.
“Our findings show the benefits of triple therapy with a budesonide–glycopyrrolate–formoterol combination over dual therapy… with respect to the annual rate of moderate or severe COPD exacerbations, symptoms, and health-related quality of life in patients with moderate-to-very-severe COPD who are at risk of exacerbations,” the researchers wrote.
“Triple therapy with a 320-μg [microgram] dose of budesonide also resulted in a lower all-cause mortality than [dual] therapy,” they added.
Mene Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, noted: “We are excited to have the data on all-cause mortality, which is a key consideration for COPD management.”